Relationship of pre-surgery metabolic and physiological MR imaging parameters to survival for patients with untreated GBM

Abstract

Glioblastoma Multiforme (GBM) are heterogeneous lesions, both in terms of their appearance on anatomic images and their response to therapy. The goal of this study was to evaluate the prognostic value of parameters derived from physiological and metabolic images of these lesions. Fifty-six patients with GBM were scanned immediately before surgical resection using conventional anatomical MR imaging and, where possible, perfusion-weighted imaging, diffusion-weighted imaging, and proton MR spectroscopic imaging. The median survival time was 517 days, with 15 patients censored. Absolute anatomic lesion volumes were not associated with survival but patients for whom the combined volume of contrast enhancement and necrosis was a large percentage of the T2 hyperintense lesion had relatively poor survival. Other volumetric parameters linked with less favorable survival were the volume of the region with elevated choline to N-acetylaspartate index (CNI) and the volume within the T2 lesion that had apparent diffusion coefficient (ADC) less than 1.5 times that in white matter. Intensity parameters associated with survival were the maximum and the sum of levels of lactate and of lipid within the CNI lesion, as well as the magnitude of the 10th percentile of the normalized ADC within the contrast-enhancing lesion. Patients whose imaging parameters indicating that lesions with a relatively large percentage with breakdown of the blood brain barrier or necrosis, large regions with abnormal metabolism or areas with restricted diffusion have relatively poor survival. These parameters may provide useful information for predicting outcome and for the stratification of patients into high or low risk groups for clinical trials.

Fig. 1

Kaplan Meier survival curves for 56 patients who were studied with MR prior to surgery and who had a diagnosis of GBM. The overall median survival (a) was 517 days, median age 56 years with a range of 26–83. Survival curves (b) are for populations split based upon the volume of ADC > 1.5 in the T2 lesion (median survival of 735 days for patients with volumes <31.6 cc, 403 days with volume > 31.6 cc), (c) are split based upon the number of voxels with CNI > 2 (median survival of 689 days for smaller volumes and 442 days for larger volumes) and (d) are split based upon the value of the sum of lipid peaks in the region with CNI > 2 region (median survival 374 days for large values and 603 days for smaller values)

Fig. 2

Post-contrast T1-weighted, T2-weighted, nCBV and ADC images from patients with GBM who had large %CEL + NEC and had relatively poor outcome. Patient A had a survival of 116 days, age = 53, %CEL = 17, %NEC = 16, T2all volume = 67 cc and nADC10%(CEL) = 1.13. Patient B had a survival of 267 days, age = 71, %CEL = 24, %NEC = 1, T2all volume = 142 cc and nADC10%(CEL) = 1.00

Fig. 3

T1-weighted post-contrast images from three patients with GBM and arrays of concentration time curves showing the spatial distribution and magnitude of peak height and recovery parameters. Patient B on the left had survival of 267 days and age = 49 with the 10th percentile of %REC = 57 and 90th percentile of nCBV = 6.0. Patient C in the center had survival of 648 days and age = 49 with the 10th percentile of %REC = 72 and 90th percentile of nCBV = 6.4. Patient D on the right had a survival >1,361 days and age of 54 with the 10th percentile of %REC = 70 and 90th percentile of nCBV = 3.7

Fig. 4

Post-contrast T1-weighted, T2-weighted, nCBV and ADC images from patients C and D from Fig. 3 who had relatively long survival. Both patients had elevated nCBV but the ADC values within the CEL volume was larger than for patients A and B from Fig. 1. Patient C, who was assessed as receiving a gross total resection, had a survival of 658 days, age = 49, %CEL = 14, %NEC = 8, T2ALL volume = 104 cc and nADC10%(CEL) = 1.30. Patient D had a survival >1,361 days, age = 54, %CEL = 27, %NEC = 16, T2ALL volume = 92 cc and nADC10%(CEL) = 1.24

Fig. 5

MR images and spectra from patients with GBM who had large number of voxels with elevated CNI outside the CEL. Reading from left to right the peaks observed are choline, creatine, NAA, and lipid. Voxels in blue have CNI > 2, voxels in red have both CNI > 2 and elevated lipid. Patient E had survival of 906 days, age = 56, number of CNI voxels > 2 = 49 and number with elevated lipid = 3. Patient F had survival of 907 days, age = 582, number of CNI voxels > 2 = 53 and number with elevated lipid = 5. Patient G had survival of 104 days, age = 63, number of CNI voxels > 2 = 58 and number with elevated lipid = 43

Fig. 6

MR images and spectra from a patient (E) who had a GBM with a large T2 volume but small enhancing lesion. Voxels in blue had CNI > 2, voxels in red had CNI > 2 with elevated lipid, voxels in yellow had elevated lipid but CNI value less than 2. For this patient age = 65, survival > 1,161 days, number of voxels with CNI > 2 = 7, number of voxels with elevated lip = 13, none with elevated lactate, sum of lipid intensities in CNI > 2 = 2.48, 10th percentile of nADC in the CEL = 1.17, %CEL + NEC = 15, T2ALL volume = 139 cc

Fig. 7

MR images and spectra from a patient (F) who had a GBM with a large T2 volume, relatively large enhancing lesion but a large number of voxels having abnormal CNI and elevated lipid and lactate. Voxels in blue had CNI > 2, voxels in red had CNI > 2 with elevated lipid, voxels in yellow had elevated lipid but CNI value less than 2. For this patient age = 62, survival 558 days, number of voxels with CNI > 2 = 42, number of voxels with elevated lip = 42, sum of lipid intensities in CNI > 2 = 17.4, 10th percentile of nADC in the CEL = 1.13, %CEL + NEC = 27, T2ALL volume = 134 cc

Fig. 8

MR images and spectra from a patient (G) who had a GBM with a moderate T2 volume, relatively larger proportion of the lesion that was enhancing or necrotic and large number of voxels with elevated CNI and lipid. For this patient age = 59, survival 104 days, voxels with CNI > 2 = 80, number of voxels with elevated lip = 45, sum of lipid intensities in CNI > 2 = 54.5, 10th percentile of nADC in the CEL = 0.91, %CEL + NEC = 66, T2ALL volume = 50 cc