SS 1011a - Brain tumours: imaging techniques
Incidences of tumour progression and treatment-induced pseudoprogression in high-grade gliomas, a systematic review and meta-analysis.
Purpose: High-grade gliomas are the most common primary brain tumours. Treatment-induced pseudoprogression describes the false appearance of radiation-induced progression on MRI. Differentiation should be made between true tumour progression to correctly plan treatment. However, there is wide variation of reported pseudoprogression. We thus aimed to establish the incidence of treatment-induced pseudoprogression and tumour progression in high-grade glioma patients with a systematic review and meta-analysis.
Methods and Materials: We searched PubMed, Embase, and Web of Science on the incidence of treatment induced pseudoprogression and tumour progression in adult high-grade glioma patients from 2005. Histology or imaging follow-up was used as reference standard. Extracted data included number of patients with progression on T1 post-contrast and/or T2/FLAIR, treatment-induced pseudoprogression and tumour progression. Study quality was assessed with the NIH Tool. Heterogeneity was tested with the chi-square and I2. Pooling of the results was done with random models using metaprop in STATA.
Results: We identified 73 studies. MRI progression occurred in 2603 patients. Of these, 36%, (95%CI 33-40%) demonstrated treatment-induced pseudoprogression, 60% (95%CI 56-64%) tumour progression and unknown outcome was present in the remaining 4% (range 1-37%).
Conclusion: We demonstrated a higher than previously thought incidence of treatment induced progression. This highlighted the full extent of the limitation of conventional MRI as currently used in the RANO criteria for treatment evaluation in high-grade gliomas. The need for more accurate treatment response evaluation using advanced imaging to aid in greater diagnostic accuracy and more accurate therapeutic approach is underscored.
Purpose: To analyse MR perfusion of the closest peritumoural oedema tumour to normal white matter in patients with glioblastoma or unique brain metastasis.
Methods and Materials: The study was conducted on patients diagnosed with brain tumours between January 2010 and December 2015, 15 GBM and 15 metastases, with histopathologic confirmation. We analysed for each area of oedema the CBV, CBF, MTT, Ktrans, ve and Kep. All perfusion biomarkers were normalised against the white matter contra-lateral unaffected by the lesion.
Results: The results show a greater heterogeneity in peritumoural oedema area in GBM patients relative to oedema concerning patients with metastases. A gradual retreat is observed in perfusion parameters of the oedema, much more pronounced in cases of GBM.
Conclusion: This work supports the hypothesis of GBM tumour infiltration in the perilesional oedema, distal to the area of enhancement.
Diffusion tensor imaging metrics as a tool for the grading of cerebral gliomas with histopathological correlation
Purpose: To evaluate the role of quantitative diffusion tensor imaging measurements including, fractional anisotropy (FA) and mean diffusivity (MD) values in the grading of cerebral glioma.
Methods and Materials: 11 patients with gliomas of low histological grades (WHO grade I and II) and 15 patients with high histological grades gliomas (WHO grade III and IV) were examined by MRI 1.5T. Mean FA, FA tumour/normal tissue ratio in the solid tumour components and corresponding mean MD, MD tumour/normal tissue ratio were measured and compared statistically among different tumour grades.
Results: There was statistically significant difference in mean FA values and FA ratios between low grade gliomas (LGGs) and high grade gliomas (HGGs). LGGs showed low FA values and ratios (mean 0.19+0.06 and 0.40+0.07, respectively) compared to that of HGGs (mean 0.35+0.06 and 0.56+0.08, respectively) p<0.001. Mean MD values and ratios were significantly higher in LGGs (mean 1.49+0.47 and 1.95+0.64, respectively) than that of HGGs (mean 1.10+0.23 and 1.43+ 0.36, respectively) p<0.010 and 0.013 respectively.
Conclusion: MR diffusion tensor imaging metrics could increase the diagnostic accuracy in the preoperative grading of cerebral glioma.
Diffusion-weighted imaging for predicting and monitoring primary central nervous system lymphoma treatment response
Purpose: This study assessed the minimum ADC correlated with treatment response in patients with primary central nervous system lymphoma undergoing methotrexate-based chemotherapy.
Methods and Materials: Thirty-five patients with primary central nervous system lymphoma underwent conventional MR imaging and DWI before chemotherapy and after 1 and 5 cycles of chemotherapy.Pretreatment minimum ADC, minimum ADC after 1 cycle, minimum ADC after 5 cycles, and change in minimum ADC were compared among the different response groups.The Pearson correlation test was calculated between these ADC parameters and tumour response.
Results: The pretreatment minimum ADC of the progressive disease group was lower than that of the complete response and partial response groups, but there was no significant difference among them. A comparison among groups showed that Minimum ADC after 1 cycle, minimum ADC after 5 cycles, minimum ADC change, and the percentage of minimum ADC change were all significantly different among the 3 groups. A significant positive correlation was observed between the percentage of minimum ADC after 1 cycle of chemotherapy and the size reduction percentage after 5 cycles of chemotherapy. The minimum ADC change and the percentage of minimum ADC change performed better in the differentiation of the final treatment response, specifically in complete response and partial response from progressive disease.
Conclusion: The minimum ADC after 1 cycle and minimum ADC changes were better correlated with the treatment response than the pretreatment minimum ADC. Minimum ADC after early therapy may potentially to be used to predict and monitor the response of primary central nervous system lymphoma to chemotherapy.
Tumour recurrence vs treatment effects in glioma: a comparative study of three dimensional pseudo-continuous arterial spin labelling and dynamic susceptibility contrast imaging
Purpose: The purpose of this study was to differentiate true progression from pseudoprogression of gliomas treated with concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ) using 3D pseudo-continuous arterial spin labelling (3D-ASL) technique and dynamic susceptibility contrast perfusion magnetic resonance imaging (DSC-MRI).
Methods and Materials: Twenty-six consecutive patients who showed new or enlarged, contrast-enhancing lesions within the radiation ﬁeld after CCRT were assessed by use of 3D-ASL and DSC-MRI. These patients were classified into groups of tumour recurrence (n=16) or pseudoprogression (n=10) based on pathologic analysis or clinical-radiologic follow-up. The extent of susceptibility artefacts in the enhanced lesions was scored from 1 to 3 (1 = no susceptibility artefacts and 3 = extensive susceptibility artefacts (maximum diameter>2 cm)). A quantitative analysis was performed with cerebral blood flow values (ASL-CBF), relative cerebral blood flow values (ASL-rCBF, DSC-rCBF) and relative cerebral blood volume values (DSC-rCBV) in the region of interest (ROI) with maximum signal enhancement.
Results: ASL had a lower susceptibility-artefact score than DSC-MRI (p=0.01). There was a statistically significant difference between tumour recurrence group and pseudoprogression group for all parameters. There was good correlation between DSC-rCBF and ASL-rCBF values, as well as DSC-rCBV and ASL-rCBF values with correlation coefficients of 0.8 and 0.727.
Conclusion: 3D-ASL is an alternative to DSC-MRI for the evaluation of perfusion in differentiating true progression from pseudoprogression of gliomas treated with CCRT. The method has fewer susceptibility artefacts than DSC-MRI and can be used in patients with renal failure because no contrast injection is needed.
Prediction of survival in patients affected by Glioblastoma multiforme evaluated with perfusion MRI: a histogram analysis
Purpose: Currently the most predictive prognostic marker for longer survival in patients with newly diagnosed glioblastoma is the MGMT promoter methylation status. The aim of this study was to verify which parameters rCBV data (kurtosis, skewness, average, maximum value, median) obtained by histogram analysis of perfusion acquisitions could predict the survival at 1 year in patients with GBM after surgical procedure.
Methods and Materials: Thirty-four patients with newly diagnosed histologically verified GBM were retrospectively evaluated. All patients received postoperative focal radiotherapy plus concomitant daily temozolomide, followed by adjuvant TMZ therapy. Each subject underwent the same MR examination with standard sequences and dynamic susceptibility-weighted contrast-enhanced perfusion. The CBVratio was then automatically calculated by the software. Histograms were generated from multiple ROIs covering the tumor and the histogram pattern was statistically evaluated for kurtosis, skewness, mean, median and maximum value of rCBV. Survival curves of histogram parameters were performed and compared to methylation status of GBM.
Results: Only kurtosis showed a significant difference comparing subjects survived more and less than a year. A significant correlation was evident between OS and rCBV kurtosis. According to ROC analysis, the rCBV kurtosis value of 1,26 represented an optimized cutoff useful to distinguish subjects survived more and less than a year. Survival curves showed a better survival condition with rCBV kurtosis more than 1,26. No similar results were appreciable in survival curves of methylated and unmethylated subjects.
Conclusion: The histogram analysis could represent a valid method to predict survival in patients affected by GBM.
Contrast-enhanced MRI vs contrast-enhanced ultrasound: a comparison in glioblastoma surgery using intra-operative fusion imaging
Purpose: To compare intraoperative contrast enhanced ultrasound (CEUS) images to the correspondent co-planar T1 weighted contrast-enhanced magnetic resonance images (gdMRI) using fusion imaging between CEUS and pre-op MRI in glioblastoma (GBM).
Methods and Materials: Ten patients with GBM diagnosis were retrospectively enrolled. All patients underwent tumor excision guided by navigated intra-operative US (ioUS) based on fusion imaging between ioUS and pre-operative MRI. Navigated CEUS scans were performed after intravenous administration of ultrasound contrast agents (CA), before tumor resection. Using fusion imaging we compared CEUS contrast enhancement (location, morphology, margins, dimensions, and pattern) to that of gdMRI.
Results: Registration between pre-operative gdMRI and ioUS demonstrated an error less the 2mm. In all cases CEUS highlighted the lesion. Contrast enhancement of gdMRI and CEUS was superimposable in all cases for location, margins, dimensions, and morphology while the pattern was the same in 9/10 cases; in one case the pattern was different.
Conclusion: CEUS contrast enhancement location, margins, morphology, and dimensions are superimposable to that provided by pre-operative gdMRI in all cases; while the pattern is the same in most of the cases. Taking into account that the goal of GBM resection is to remove all the gdMRI enhanced area, the information obtained with CEUS are of paramount importance in surgical management of GBM.
Could new reconstruction CT techniques challenge MRI for the detection of brain metastasis in the context of initial lung cancer staging?
Purpose: To evaluate the diagnostic performance of brain CT images reconstructed with a model-based iterative algorithm and acquired at conventional and reduced dose in the staging work-up of lung cancer.
Methods and Materials: 115 patients with histologically proven lung cancer were prospectively included between July 2014 and September 2015. Patients underwent 2 brain CT acquisitions, during the same initial staging session. Acquisitions were performed on a 256-slice MDCT (Philips Healthcare, Cleveland OH) at standard (CTDIvol: 41.4mGy) and half dose (CTDIvol: 20.7mGy). Both images datasets were reconstructed with Filtered Back Projection (FBP) and model-based iterative reconstruction algorithm (IMR, Philips HealthCare, OH). Brain MRI was performed within 7 days and was considered as the gold standard. 2 blinded independent readers analysed the images. Diagnostic performance and inter-observer agreement were calculated.
Results: 93 patients underwent all examinations. MRI showed 56 metastasis on 17 patients. At the standard dose, 8 patients presented metastasis on both FBP and IMR CT images with 15 and 17 lesions, respectively. At half-dose, 6 (FBP) and 7 patients (IMR), presented 13 and 15 lesions, respectively. Specificity, negative and positive predictive values were excellent for all CT techniques.The test couldn't highlight any significant difference between the standard dose IMR and the half dose FBP techniques (p=0.12>0.05).
Conclusion: Even using new CT reconstructions techniques, MRI is still the best imaging tool to detect brain metastases at the initial staging of lung cancer. No significant difference could be demonstrated between the 2 CT techniques.
Exact differentiation of tumoural borders in patients with glioma by MRS and diffusion magnetic resonance imaging
Purpose: Most of patients with glioma are planned for surgical intervention in whom, exact localisation of tumour borders is so critical as this could optimize the surgery to remove as much as tissues involved by tumour and preserve intact tissues. Here, we want to assess the exact differentiation of tissues involved by glial tumoural cells vs non-involved areas by MRS and perfusion MRI.
Methods and Materials: Ten patients with glioma diagnosis based on conventional MRI features were enrolled [mean age: 35.3±13.2, range: 20-62, 6 males]. All patients underwent 3T MRI in which tumour mapping based on MRS was featured and according to this mapping, different tumoural and peritumoural locations [including tumoural core, infiltrative oedema, reactive oedema and normal tissue] were determined. Quantitative diffusion and MRS measurements on these locations were performed. Then, using a biopsy navigation system, biopsies were taken from different mentioned locations and histopathological assessment results were considered as gold standard. MRI quantitative measurements of different locations were compared together.
Results: Among 48 pathologic samples,36 (75%) contained tumoural cells [including 9 tumoural core, 26 infiltrative tissues and 1 necrosis]. Based on primary mapping, 7 (19.4%) of these positive samples were missed [five were diagnosed as reactive oedema and 2 as normal tissue] [kappa: 0.67, P value<0.001]. Mean of ADC was statistically higher in tumoural samples (P=0.002). Median of NAA and NAA/Chol was different between positive and negative samples (P value<0.001). Mean ADC and median Chol/NAA were statistically different in missed reactive oedema samples than normal and correctly diagnosed reactive oedema samples together (P values <0.05).
Conclusion: Detailed diffusion and MRS quantitative measurements could be new measurements for more exact delineating peritumoural borders of gliomas.
Purpose: Proton radiotherapy is an effective modality for the treatment of paediatric brainstem tumours. Many tumours including tectal gliomas may respond to proton radiotherapy initially by increasing in size that may be misinterpreted as tumour progression. The purpose of our study is to assess the quantitative response of tectal gliomas by performing serial MRI measurements of tumour volume over time to identify a predictable trend in tumour response to proton radiotherapy.
Methods and Materials: Following IRB approval, a retrospective clinical database search was performed for patients with tectal gliomas. Patients aged 0 through 25 years with tectal gliomas who underwent proton radiotherapy were included. Patients with tumours previously treated with radiotherapy or surgical resection were excluded. Cubic volume measurements were obtained from FLAIR MRI scans at all available timepoints.
Results: Five subjects met inclusion criteria with median age 14.4 years (average, 16.2 years; range, 12.6-20.8 years). Median imaging follow-up was 2.6 years (average, 3.0 years; range, 1.4-5.4 years) with a median of 8 post-treatment timepoints (average, 7.6; range, 4-10). Each of the five tumours followed a pattern of post-radiotherapy enlargement followed by reduction in size. The peak tumour volume occurred at a median of 6.9 months (average, 6.2 months; range, 3.5-8.2 months) from initiation of radiotherapy.
Conclusion: Following proton radiotherapy, tectal gliomas demonstrate a predictable trend of enlargement and subsequent reduction in tumour size. This trend may be helpful in distinguishing radiographic response from tumour progression.