Role of functional MRI in evaluating intraaxial brain tumors Advances and pitfalls.

Transcription

1 Role of functional MRI in evaluating intraaxial brain tumors Advances and pitfalls. Poster No.: C-1685 Congress: ECR 2014 Type: Educational Exhibit Authors: A. R. Udare, A. Mahajan, S. Juvekar, P. Shetty, M. H. Thakur, A. Moidayi ; Mumbai/IN, MUMBAI, MAHARASHTRA/IN Keywords: Cancer, Staging, Imaging sequences, MR-Functional imaging, MR-Diffusion/Perfusion, MR, Oncology, Neuroradiology brain, Molecular imaging DOI: /ecr2014/C-1685 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 21

2 Learning objectives 1. Provide an overview of newer functional MRI techniques including DWI, Perfusion, DTI and MRS including a basic understanding of the physics of these imaging sequences. 2. To evaluate the role of these functional MR techniques in pre-operative characterization of intra-axial brain tumors 3. Evaluate role of volumetric measurements in pre and post operative assessment of tumors 4. Described limitations and pitfalls of the above techniques. Background Gliomas are the most common primary brain tumors accounting for 28% of all brain tumors and 80% of malignant tumors [1]. Glioblastoma Multiforme (GBM) is classified as a Grade IV glioma and counts for 45% of all malignant CNS tumors [1]. Inspite of recent advances in surgical techniques, radiotherapy and chemotherapy, the mean survival in these patients is 12 months [2]. The current standard of imaging for brain tumors is Magnetic Resonance Imaging (MRI). Routine MRI sequences like T1W, T2W, FLAIR (Fluid Attenuated Inversion Recovery) and post contrast sequences provide us excellent details regarding the morphology and extent of disease. However it is not possible to differentiate between high grade gliomas and low grade gliomas using these conventional sequences. Although the current standard for grading is histopathological assessment, it has its own set of limitations as only a small portion of the tumor is sampled and the most aggressive portion may not be included in this sample thus underestimating the grade of the tumor. Also post operatively it is often difficult to distinguish treatment related changes (psuedoprogression) and progression on conventional imaging. Advanced functional imaging tools such as Magnetic Resonance Spectroscopy (MRS), Diffusion Weighted Imaging (DWI) and perfusion imaging are complimentary to conventional imaging sequences and provide us an insight into the molecular composition and help predict the tumor grade. Diffusion Tensor Page 2 of 21

3 Imaging (DTI) helps surgical planning. These sequences can be readily integrated into the already available hardware hence no new installation is required. Findings and procedure details The following features will be reviewed MR spectroscopy: Choline/NAA, Choline/Creatine ratios and metabolite maps DWI analysis including ADC values and signal intensities on DWI. Perfusion parameters: Relative cerebral blood flow and volume, Mean Transit Time and Time to peak Volumetric analysis of intra-axial tumors Role of DTI in surgical planning. MR Spectroscopy (MRS). MRS allows a non-invasive qualitative and quantitative analysis of certain metabolites in the brain. It is used to detect metabolic abnormalities in the tumor and in the peritumoral region which often precede structural changes. In a typical MRS graph, the horizontal X axis displays the chemical shift of metabolites in parts per million and the vertical Y axis shows the signal amplitude corresponding to the relative concentration of the metabolite. The various metabolites are identified by their peculiar chemical shift. The commonly studied metabolites and their normal role and pathological significance are shown.( Table 1 on page 18 ) [3]. High grade gliomas are characterized by elevated Choline, decreased NAA, and elevated lipid and lactate levels while elevation of myoinositol is a feature seen in low grade gliomas [4]. A choline/naa cutoff ratio of 2.2 can be used to separate high-grade neoplasms from low-grade neoplasms and non-neoplastic conditions [4]. Page 3 of 21

4 Fig. 1: Conventional MRI brain axial images show a relatively well defined lesion in right parieto-occipital region with minimal peritumoral edema and intense post contrast enhancement. It is difficult to comment upon the grade of the tumor accurately on these images. References: Radiodiagnosis, Tata Memorial Hospital, Tata Memorial Hospital Mumbai/IN Page 4 of 21

5 Fig. 2: MR spectroscopy carried out at TE 144ms (post-processed image) in the same lesion as seen in Fig 1 shows markedly elevated Ch/NAA in the lesion seen as red on the color coded maps. References: Radiodiagnosis, Tata Memorial Hospital, Tata Memorial Hospital Mumbai/IN Page 5 of 21

6 Fig. 3: Graphs showing elevated choline and decreased NAA with elevated choline/ creatine (4.4:1 and 5.5:1) and choline/naa ratio (7.8:1 and 5.6:1)in voxels 2 and 7 respectively. References: Radiodiagnosis, Tata Memorial Hospital, Tata Memorial Hospital Mumbai/IN Diffusion Weighted Imaging DWI examines the motion of water molecules, which is normally random or Brownian. The greater the density of structures that impede water mobility, the lower the ADC. ADC is considered a non-invasive indicator of cellularity or cell density [5]. Necrotic regions have the highest ADC values due the low cellularity while the low ADC values are seen in the highly cellular contrast enhancing component of the tumor [5] Page 6 of 21

7 The ADC is found to be inversely proportional to the grade of the tumor[5]. Low-grade astrocytoma has high ADC values, whereas high grade malignant glioma has low ADC values Also a very low ADC value is suggestive of a highly cellular tumor like lymphoma or metastasis rather than a glioma. However the ADC values may not be always elevated in high grade gliomas and this needs to be interpreted with caution as is seen in Fig. 4 on page 15 Fig. 4: DWI and ADC maps in the lesion seen in Fig 1 show no significant restriction of diffusion although it was a high grade glioma. Comparison has been made with opposite normal side. References: Radiodiagnosis, Tata Memorial Hospital, Tata Memorial Hospital Mumbai/IN Page 7 of 21

8 Fig. 5: Conventional MRI brain axial images show a relatively well defined lesion in left parietal lobe with mild peripheral enhancement minimal perilesional edema References: Radiodiagnosis, Tata Memorial Hospital, Tata Memorial Hospital Mumbai/IN Fig. 6: DWI and ADC map in the lesion in Fig 5 show restriction of diffusion in the posterior aspect of the lesion as compared to opposite normal brain parenchyma suggestive of high cellularity. The absolute ADC value is 0.6 x 10-3 mm2/s while the relative ADC value as compared to opposite brain is 78% References: Radiodiagnosis, Tata Memorial Hospital, Tata Memorial Hospital Mumbai/IN Page 8 of 21

9 Perfusion Imaging Perfusion Imaging helps us to identify neoangiogenesis and capillary permeability in tumors. Neoplastic tissue often outgrows its blood supply and is then supplied by structurally abnormal, fragile vessels which have increased permeability. The most commonly employed method for studying perfusion in brain tumors is T2*-weighted first-pass, dynamic susceptibility contrastenhanced perfusion MRI (DSC MRI). In this, a gadolinium based contrast material is injected using a pressure injector at a constant rate. This induces susceptibility T2* effect which are plotted against time on the X axis to give the susceptibility-signal intensity curve. Various parameters can be acquired by post processing of the acquired data set including relative cerebral blood flow (rcbf), relative cerebral blood volume (rcbv), mean time to transit (MTT) and time to peak (TTP). These are processed by placing a region of interest in the tumor and comparing it with an area of normal brain parenchyma. Out of these, the rcbv(relative cerebral blood volume) is found to correlate well with the tumor grade [4,5]. An absolute value of rcbv > 1.75 can be used to as a cutoff threshold to distinguish a high grade tumor from a low-grade tumor. It is important to note that a subset of oligodendrogliomas can also have high perfusion parameters [4, 6] Perfusion imaging can also be used to distinguish between gliomas and metastasis. Gliomas, especially the high grade gliomas have an infiltrative component. It is found that perituomral rcbv values are significantly higher in primary brain tumors than metastasis [7]. Perfusion is also helpful in differentiating treatment induced enhancement (pseudoprogression) from true progression of disease [8]. Tumor related enhancement is associated with significantly higher rcbv than that seen with treatment related changes [8]. Page 9 of 21

10 Fig. 7: Dynamic susceptibility contrast (DSC) MRI perfusion (post-processed images) in the lesion seen in Fig 1 shows significant elevation of relative cerebral blood flow (rcbv =2.34:1) and relative cerebral blood volume (rcbf= 3.43:1). Mild elevation of the time to peak (TTP) and Mean transit time (MTT) is also seen. The perfusion curve shows intense rapid enhancement in the involved lesion (purple curve) References: Radiodiagnosis, Tata Memorial Hospital, Tata Memorial Hospital Mumbai/IN Fig. 8: Dynamic susceptibility contrast (DSC) MRI perfusion and MRS at 144TE in lesion seen in Fig 5. There is elevation of rcbf (3.47:1) and rcbv (2.88:1) in the medial aspect of the lesion which also shows elevated Ch/NAA ratio suggestive of a high grade lesion. References: Radiodiagnosis, Tata Memorial Hospital, Tata Memorial Hospital Mumbai/IN Volumetric Analysis Page 10 of 21

11 Until now brain tumor trials used the MacDonald's two dimensional criteria for estimation of tumor burden. However with the advent of semi-automatic and automatic volumetric methods, the trend is shifting towards volumetric measurements as these are able to provide more accurate information about the tumor load. Immediate post-op period residual tumor volume has prognostic significance on the time to tumor progression (TTP) and overall survival (OS) [9]. Fig. 9: Determination of preoperative tumor volume in three different planes using thin section 3D FSPGR sequences and semi-automated technique References: Radiodiagnosis, Tata Memorial Hospital, Tata Memorial Hospital Mumbai/IN Diffusion Tensor Imaging. Diffusion tensor imaging uses diffusion measurements in multiple directions and tensor decomposition to extract the diffusivities parallel and perpendicular to the white matter fiber tracts. In white matter tracts anisotropy is high due to the fast diffusibility along the fiber tracts and significantly lower in directions perpendicular to them [10]. On the other hand the movement of water molecules is random in gray matter and CSF, hence diffusivity is similar in all directions and anisotropy is very low[10]. This can be depicted on 2D imaging as Fractional Anisotropy (FA) maps. The information acquired can also be used to produce 3D visual trajectories which can be used in determining whether the white matter fiber tracts are displaced or involved by the tumor process. Page 11 of 21

12 Fig. 10: Diffusion tract Imaging (post processed) shows the mass in the left parietal lobe (arrow) displacing the eloquent fiber tracts. Conventional T2 and post contrast images are given alongside for reference References: Radiodiagnosis, Tata Memorial Hospital, Tata Memorial Hospital Mumbai/IN Newer guidelines for imaging in response assessment of gliomas: The Response Assessment in Neuro-Oncology (RANO) Working Group recently published new response and progression criteria for the assessment of the effects of surgery and surgically delivered therapies for patients with gliomas [11]. Some of the key guidelines are [11] To avoid interpretation of postoperative changes as residual (or new) enhancing disease, a baseline MR imaging (MRI) scan with and without gadolinium contrast enhancement should ideally be obtained within 24 to 48 hours after surgery and no later than 72 hours after surgery. In the case of low grade gliomas, which usually do not show post contrast enhancement, a complete surgical resection often involves removal of all of the disease defined by T2 or fluid-attenuated inversion recovery (FLAIR) imaging seen on preoperative imaging. In cases when enhancement is present, removal of all enhancing tissue should be called complete resection of enhancing tumor rather than gross total resection. Page 12 of 21

13 Future evaluations of completeness of resection should focus on the actual volumes of residual enhancing and/or nonenhancing tumor. Images for this section: Fig. 1: Conventional MRI brain axial images show a relatively well defined lesion in right parieto-occipital region with minimal peritumoral edema and intense post contrast enhancement. It is difficult to comment upon the grade of the tumor accurately on these images. Page 13 of 21

14 Fig. 2: MR spectroscopy carried out at TE 144ms (post-processed image) in the same lesion as seen in Fig 1 shows markedly elevated Ch/NAA in the lesion seen as red on the color coded maps. Page 14 of 21

15 Fig. 3: Graphs showing elevated choline and decreased NAA with elevated choline/ creatine (4.4:1 and 5.5:1) and choline/naa ratio (7.8:1 and 5.6:1)in voxels 2 and 7 respectively. Page 15 of 21

16 Fig. 4: DWI and ADC maps in the lesion seen in Fig 1 show no significant restriction of diffusion although it was a high grade glioma. Comparison has been made with opposite normal side. Fig. 5: Conventional MRI brain axial images show a relatively well defined lesion in left parietal lobe with mild peripheral enhancement minimal perilesional edema Fig. 6: DWI and ADC map in the lesion in Fig 5 show restriction of diffusion in the posterior aspect of the lesion as compared to opposite normal brain parenchyma suggestive of high cellularity. The absolute ADC value is 0.6 x 10-3 mm2/s while the relative ADC value as compared to opposite brain is 78% Page 16 of 21

17 Fig. 7: Dynamic susceptibility contrast (DSC) MRI perfusion (post-processed images) in the lesion seen in Fig 1 shows significant elevation of relative cerebral blood flow (rcbv =2.34:1) and relative cerebral blood volume (rcbf= 3.43:1). Mild elevation of the time to peak (TTP) and Mean transit time (MTT) is also seen. The perfusion curve shows intense rapid enhancement in the involved lesion (purple curve) Fig. 8: Dynamic susceptibility contrast (DSC) MRI perfusion and MRS at 144TE in lesion seen in Fig 5. There is elevation of rcbf (3.47:1) and rcbv (2.88:1) in the medial aspect of the lesion which also shows elevated Ch/NAA ratio suggestive of a high grade lesion. Page 17 of 21

18 Fig. 9: Determination of preoperative tumor volume in three different planes using thin section 3D FSPGR sequences and semi-automated technique Fig. 10: Diffusion tract Imaging (post processed) shows the mass in the left parietal lobe (arrow) displacing the eloquent fiber tracts. Conventional T2 and post contrast images are given alongside for reference Page 18 of 21

19 Table 1: Routine metabolites in MR spectroscopy of intra-axial brain tumors Page 19 of 21

20 Conclusion Advanced functional MR imaging sequences are thus valuable for: Making a specific diagnosis, determination of histologic grade, guiding biopsies, therapeutic planning, and to monitor patients after treatment. Evaluate hemodynamic properties of the tumor such as tumor blood volume or blood flow, oxygenation, vessel size, and vascular permeability. Assessing the integrity of white mater tracts and for preoperative planning for brain tumors in and around eloquent white matter tracts. Functional MRI can provide additional insights into the biochemical make-up of tumors and help us in predicting the prognosis and in formulating treatment protocols and monitoring treatment in gliomas. Hence these should be routinely integrated in the imaging work-up of all intra-axial brain tumors. Personal information A. R. Udare, A.Mahajan, S.Juvekar, M.H. Thakur: Department of Radiodianosis A. Moidayi, P.Shetty : Department of Neurosurgery id : amarudare@gmail.com Institute: Tata Momorial Hospital, Parel Mumbai India Page 20 of 21

21 References 1. Ostrom, Q. T., Gittleman, H., Farah, P et al. CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in Neuro-oncology, 15(suppl 2), ii1-ii Mrugala M. M. Advances and challenges in the treatment of glioblastoma: a clinician's perspective. Discovery medicine 15, (2013). 3. Soares DP, Law M (2009) Magnetic resonance spectroscopy of the brain: Review of metabolites and clinical applications. Clin Radiol 64: Al-Okaili RN, Krejza J, Wang S, Woo JH, Melhem ER. Advanced MR imaging techniques in the diagnosis of intraaxial brain tumors in adults. RadioGraphics 2006; 26(suppl 1):S173-S Law M, Yang S, Wang H, et al. Glioma grading: sensitivity, specificity, and predictive values of perfusion MR imaging and proton MR spectroscopic imaging compared with conventional MR imaging. AJNR Am J Neuroradiol 2003;24(10): Lev MH, Ozsunar Y, Henson JW, et al. Glial tumor grading and outcome prediction using dynamic spin-echo MR susceptibility mapping compared with conventional contrast-enhanced MR: confounding effect of elevated rcbv of oligodendrogliomas. AJNR Am J Neuroradiol 2004; 25: Law M, Cha S, Knopp EA, Johnson G, Arnett J, Litt AW. High-grade gliomas and solitary metastases: differentiation by using perfusion and proton spectroscopic MR imaging. Radiology Mar;222(3): Young RJ, Gupta A, Shah AD, Graber JJ, Chan TA, Zhang Z, et al. MRI perfusion in determining psuedoprogression in patients with glioblastoma. Clin Imaging. 2013;37: Keles GE, Chang EF, Lamborn KR, et al. Volumetric extent of resection and residual contrast enhancement on initial surgery as predictors of outcome in adult patients with hemispheric anaplastic astrocytoma. J Neurosurg. 2006;105: Assaf Y, Pasternak O. Diffusion tensor imaging (DTI)-based white matter mapping in brain research: a review. J Mol Neurosci 2008;34: Vogelbaum MA, Jost S, Aghi MK, Heimberger AB, Sampson JH, Wen PY, Macdonald DR, Van den Bent MJ, Chang SM. Application of novel response/progression measures for surgically delivered therapies for gliomas: Response Assessment in Neuro-Oncology (RANO) Working Group. Neurosurgery Jan;70(1):234-43; discussion Page 21 of 21