Goals for this Lecture. Case 1. Key Points MRI TECHNIQUES FOR DIFFERENTIAL DIAGNOSIS OF RECURRENT BRAIN LESIONS

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1 MRI TECHNIQUES FOR DIFFERENTIAL DIAGNOSIS OF RECURRENT BRAIN LESIONS Goals for this Lecture 1. Review common appearances for recurrent tumor and treatment effects on conventional MRI 2. Discuss current roles and limitations of anatomic MRI methods for assessing response versus recurrence 3. Outline the rationale for and practical application of physiologic MRI methods for problem solving Christopher P. Hess, M.D., Ph.D. Assistant Professor, Radiology & Biomedical Imaging Neuroradiology Chief, San Francisco VA Medical Center University of California, San Francisco Diffusionweighted MRI MR Perfusion Proton MR Spectrosopy Key Points Case 1 Never interpret imaging without treatment history and prior studies Anatomic MRI is very sensitive for assessing response to treatment, but has important shortcomings Before Physiologic MRI techniques can help... sometimes Antiangiogenic agents are game changers After

2 Case 2 Progression True Progression Pseudoprogression Before MRI Gad T1 Diffusion Perfusion Spectroscopy After Pseudoresponse Response True Response Treatment Response, 1990: Macdonald Criteria Macdonald et al, J Clin Oncol 1990; 8: Enhancement: Strengths Most high grade tumor enhances First objective criteria used for assessment of treatment response, enabled crosstrial comparison 4 categories: complete response, partial response, stable disease, progression 3 metrics, only 1 based on imaging Use of corticosteroids Changes in neurological status Enhancing tumor area = Weaknesses Measurement difficult when shape irregular Altered by MRI technique Modulated by medications Ignores multifocal tumor

3 Enhancement: Weaknesses (continued) Not all tumor enhances Cystic / necrotic tumor Infiltrative tumor Lowgrade tumor Enhancement: Reflects disruption of BBB from any cause Recurrence Radiation Necrosis Infarct Helpful Enhancement Patterns Treatment Mullins et al, AJNR 2005; 26: Kumar et al, Radiology 2000; 217: Recurrent Tumor Spread through corpus callosum Subependymal enhancement Enhancement in originally nonenhancing tumor Enhancement within port but remote from original tumor Periventricular location Soap bubble or Swiss chesse pattern Enhancement crossing through corpus callosum Subependymal enhancement Multiple solid enhancing lesions Multifocal enhancement

4 Postop Enhancement Soap bubbles Preop: GBM 24 hr postop: Gross total resection 2 months: Recurrence? Swiss cheese Periventricular Solution: Postop Diffusion MRI H + in CSF H + in WM H + in Infarct Diffusion MRI Reduced diffusion on 24 hr postop MRI Acute PCA Infarct DWI Courtesy Soonmee Cha, MD (UCSF Neuroradiology)

5 Timing for Postoperative MRI Ulmer et al, Neurology 2006; 67: year old with unresectable GBM 9/26 8/24 Postop MRI within first 48 hours Mass effect Postsurgical enhancement begins at 4872 hrs, imaging before this time best shows extent of resection Enhancment Diffusionweighted imaging for anticipated areas of postsurgical enhancement signal Tumor Progression? 11/31 9/26 8/24 Resection Median PFS ~ 7 mo Dx R.T. Progression

6 Resection Median PFS ~ 7 mo Classic Radiation Changes Dx Radiation R.T. Three categories of radiation encephalopathy: 1. Acute 2. Earlydelayed 3. Latedelayed Divided by time course, clinical presentation, pathology, and imaging findings Variable at each stage, depending on dose and focal versus wholebrain irradiation Earlydelayed can present diagnostic dilemma, ie pseudoprogression Pseudoprogression Chamberlain et al, J Neurooncol 2007; 82: 8182 Taal et al, Cancer 2008; 113: Brandes et al, J Clin Oncol 2008; 26: Patients treated with concurrent chemoradiation Similar to earlydelayed radiation changes but more exhuberant and earlier May also have deteriorating clinical status Up to 4749% of patients on concurrent temozolamide Methylation of MGMT promotor may predisposing to pseudoprogression

7 Pseudoprogression in a 65yearold patient with GBM Brandes et al, NeuroOncology 2008; 10: 3617 DSC Perfusion MRI A. Presurgical MRI scan. B. Postsurgical MRI scan. C. One month after combined TMZ & radio; adjuvant TMZ was continued. D. Four months later, during administration of maintenance TMZ E. Eight months later, during administration of maintenance TMZ RBC Gd Rapid T2*weighted imaging Injected gadolinium bolus modulates image intensity during bolus passage Dynamic changes in T2* intensity allow voxelwise calculation of local hemodynamic parameters Noninvasive microcirculation assessment (angiogenesis) T2* signal intensity 1000 [GdDTPA] 0.02 Tumor Perfusion Courtesy Soonmee Cha, MD (UCSF Neuroradiology)

8 Nontumor Perfusion Tumor or Radionecrosis? Tumor or Radionecrosis? Proton MR Spectroscopy Chemical shift (ppm) related to molecular composition Noninvasive assessment of metabolism CH3 Ratio 3:1 OH Chemical shift (ppm)

9 Important MRS Metabolites Normal 1 H MRS Short TE Spectroscopy Shift (ppm) Biologic Correlate Interpretation NAA 2.01 Neuronal integrity Tumor infiltration Cr 3.03 Energy available Cho 3.19 Membrane turnover Tumor proliferation Lac 1.31 Anaerobic metabolism Hypoxia Lipid Necrosis Cell death Gray matter White matter Normal 1 H MRS Long TE Spectroscopy NAA Neurons replaced / displaced High membrane turnover No necrosis or phagocytosis Cho Cr Cho Cr No Lac No Lipid T2 MRS (TE = 288 ms) NAA T2

10 Radiation Necrosis Recurrent Tumor Tumor metabolism Necrosis Lipid peaks only Perfusion & Spectroscopy Limitations 62 yearold with biopsy+ GBM 7/30 1/10 Distortion around bone, blood products, calcium, metal from surgery Mass effect Limited volume of coverage Enhancment Low signal to noise Sensitivity to motion (especially MRS) signal Sensitivity to ROI placement (especially MRP) Treatment Response?

11 Pseudoresponse Progression on Bevacizumab Norden et al, Neurology 2008; 70: Antiantigenic therapies VEGF bevacizumab (Avastin) VEGFr cediranib (Recentin) Reduce enhancement in as little as 12 days Reported radiologic response rate 2560% Little or no benefit in progressionfree survival Before After Progression on Bevacizumab Gerstner et al, J Clin Oncol 2010; 28: e91e92 DWI Treatment Response, 2010: RANO Criteria RANO Working Group, J Clin Oncol 2010: 28: Before After Same response categories as Macdonald criteria Also weighs steroid use and clinical status Considers timing of chemoradiation and isodose lines in assessment of progression versus response Omits measurement of cystic portions of tumor Considers both enhancement and signal Includes criteria for multifocal tumor

12 Treatment Response, 2010: RANO Criteria RANO Working Group, J Clin Oncol 2010: 28: Key Points Never interpret imaging without treatment history and prior studies Anatomic MRI is very sensitive for assessing response to treatment, but has important shortcomings Physiologic MRI techniques can help... sometimes Antiangiogenic agents are game changers Thank you for your attention! christopher.hess@radiology.ucsf.edu

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