Differentiation Of True Progression Research Articles

NIMG-41. ASSOCIATION BETWEEN PERFUSION IMAGING METRICS AND RADIO-PATHOMIC MAPS OF TUMOR PROBABILITY WITHIN AND BEYOND THE CONTRAST-ENHANCING VOLUME IN GLIOMA PATIENTS

Abstract Perfusion MRI, using both contrast-based techniques such as dynamic susceptibility imaging (DSC) and non-contrast-based techniques like arterial spin labeling (ASL) have been used to monitor blood flow as a marker of angiogenic glioma presence, and showed substantial potential in the differentiation of true progression from pseudoprogression post-treatment. This study uses radio-pathomic maps of cellularity sensitive to areas of non-enhancing tumor to test the hypothesis that perfusion-derived markers of tumor probability will associate with tumor presence within contrast-enhancement but not beyond the enhancing margin. This study included pre-surgical relative cerebral blood volume (rCBV) estimates derived from DSC perfusion data from the PENN-GBM dataset (n=456) and presurgical ASL images from the UCSF-PDGM dataset (n=426) for analyses. The T1, T1C, FLAIR, and ADC images from each patient were used to generate radio-pathomic cell density maps using a previously validated model that excels at accurate detection of non-enhancing tumor presence. Mean cell density, rCBV, and ASL were computed for each corresponding patient within included segmentations for contrast-enhancement (excluding necrotic core) and FLAIR hyperintensity (excluding both necrotic core and enhancement). Pearson’s correlations were then used to quantify the association between perfusion-derived estimates and mean cell density within each region of interest. Both rCBV and ASL showed positive associations with cell density within contrast enhancement (rCBV: R=0.280, p< 0.001; ASL: R=0.117, p=0.016). However, both perfusion metrics also showed no association with cell density within the non-enhancing, FLAIR hyperintense region (rCBV: R=0.0162, p=0.731; ASL: R=-0.213, p=0.634). These results suggest that perfusion imaging successfully identifies angiogenic tumor but may be less efficacious in detecting non-enhancing tumor presence. Future studies should examine how perfusion’s relationship with hypercellular tumor presence evolves in the presence of treatment, as well as in relation to other advanced imaging metrics such as MR spectroscopy and CEST imaging.

Differentiation of true progression from treatment response in high-grade glioma treated with chemoradiation: a comparison study of 3D-APTW and 3D-PcASL imaging and DWI.

To assess and compare the diagnostic performance of 3D amide proton-transfer-weighted (3D-APTW) imaging, 3D pseudocontinuous arterial spin-labeling (3D-PcASL) imaging, and diffusion-weighted imaging in distinguishing true progression (TP) from treatment response (TR) in posttreatment malignant glioma patients. Forty-eight patients with suspected tumor recurrence were prospectively enrolled. Histological or longitudinal routine MRI follow-up over six months was assessed to confirm lesion type. The apparent diffusion coefficient (ADC), relative APTWmax (rAPTW), and relative CBFmax values (rCBF) were measured in lesions with enhancing regions on post-gadolinium T1 -weighted MRI. MRI parameters between the TP and TR groups were compared using Student's t tests. In addition, a receiver operating characteristic (ROC) curve was constructed, and the area under the ROC curve (AUC) was calculated to assess the differentiation diagnostic performance of each parameter. The TP group showed a significantly higher rAPTW and rCBF than the TR group; the AUCs of rAPTW and rCBF to distinguish between TP and TR were 0.911 (with sensitivity of 90.3% and specificity of 82.4%) and 0.852 (with sensitivity of 80.6% and specificity of 82.4%), respectively. By adding the rAPTW values to rCBF values, the diagnostic ability was improved from 0.852 to 0.951. ADC showed no significant differences between the TP and TR groups, with an AUC lower than 0.70. Both 3D-PcASL and 3D-APTW imaging could distinguish TP from TR, and 3D-APTW had a better diagnostic performance. Combining the rAPTW values and rCBF values achieved a better diagnostic performance.

Combined 18F-FET PET and diffusion kurtosis MRI in posttreatment glioblastoma: differentiation of true progression from treatment-related changes.

BackgroundRadiological differentiation of tumor progression (TPR) from treatment-related changes (TRC) in pretreated glioblastoma is crucial. This study aimed to explore the diagnostic value of diffusion kurtosis MRI combined with information derived from O-(2-[18F]-fluoroethyl)-l-tyrosine (18F-FET) PET for the differentiation of TPR from TRC in patients with pretreated glioblastoma.MethodsThirty-two patients with histomolecularly defined and pretreated glioblastoma suspected of having TPR were included in this retrospective study. Twenty-one patients were included in the TPR group, and 11 patients in the TRC group, as assessed by neuropathology or clinicoradiological follow-up. Three-dimensional (3D) regions of interest were generated based on increased 18F-FET uptake using a tumor-to-brain ratio of 1.6. Furthermore, diffusion MRI kurtosis maps were obtained from the same regions of interest using co-registered 18F-FET PET images, and advanced histogram analysis of diffusion kurtosis map parameters was applied to generated 3D regions of interest. Diagnostic accuracy was analyzed by receiver operating characteristic curve analysis and combinations of PET and MRI parameters using multivariate logistic regression.ResultsParameters derived from diffusion MRI kurtosis maps show high diagnostic accuracy, up to 88%, for differentiating between TPR and TRC. Logistic regression revealed that the highest diagnostic accuracy of 94% (area under the curve, 0.97; sensitivity, 94%; specificity, 91%) was achieved by combining the maximum tumor-to-brain ratio of 18F-FET uptake and diffusion MRI kurtosis metrics.ConclusionsThe combined use of 18F-FET PET and MRI diffusion kurtosis maps appears to be a promising approach to improve the differentiation of TPR from TRC in pretreated glioblastoma and warrants further investigation.

Multiparametric MRI as a potential surrogate endpoint for decision-making in early treatment response following concurrent chemoradiotherapy in patients with newly diagnosed glioblastoma: a systematic review and meta-analysis.

To evaluate the value of multiparametric MRI for determination of early treatment response following concurrent chemoradiotherapy in patients with newly diagnosed glioblastoma. A computerized search of Ovid-MEDLINE and EMBASE up to 1 October 2017 was performed to find studies on the diagnostic performance of multiparametric MRI for differentiating true progression from pseudoprogression. The beginning search date was not specified. Pooled estimates of sensitivity and specificity were obtained using hierarchical logistic regression modeling. We performed meta-regression and sensitivity analyses to explain the effects of the study heterogeneity. Nine studies including 456 patients were included. Pooled sensitivity and specificity were 84 % (95 % CI 74-91) and 95 % (95 % CI 83-99), respectively. Area under the hierarchical summary receiver operating characteristic curve was 0.95 (95 % CI 0.92-0.96). Meta-regression showed true progression in the study population, the mean age and the reference standard were significant factors affecting heterogeneity. Multiparametric MRI may be used as a potential surrogate endpoint for assessment of early treatment response, especially in the differentiation of true progression from pseudoprogression. However, based on the current evidence, monoparametric and multiparametric MRI perform equally in the clinical context. Further evaluation will be needed. • Multiparametric MRI shows high diagnostic performance for early treatment response in glioblastoma. • Multiparametric MRI could differentiate true progression from pseudoprogression in newly diagnosed glioblastoma. • The normalized rCBV derived from DSC was the most commonly used parameter.

Differentiation of true-progression from pseudoprogression in glioblastoma treated with radiation therapy and concomitant temozolomide by GLCM texture analysis of conventional MRI

Twenty-two patients with pathologically confirmed glioblastoma who had received concurrent CCRT with TMZ underwent conventional MRI including T1-weighted imaging(T1WI), T2-weighted imaging(T2WI), fluid attenuated inversion recovery(FLAIR)and contrast-enhanced T1WI(T1Ce). Five GLCM texture maps of contrast, energy, entropy, correlation and homogeneity were generated for each MRI series. Of the aforementioned 5 texture features, the most significant features were contrast and correlation on T2WI with areas under ROC curve of 0.883 and 0.892, respectively, and they had the same sensitivity of 75%, specificity of 100%, accuracy of 86.4%, PPV of 100% and NPV of 76.9% in differentiation true progression from pseudoprogression.

Differentiation of True Progression from Pseudoprogression in Glioblastoma Treated with Radiation Therapy and Concomitant Temozolomide: Comparison Study of Standard and High-b-Value Diffusion-weighted Imaging

Purpose To explore the role of histogram analysis of apparent diffusion coefficient (ADC) maps obtained at standard- and high-b-value (1000 and 3000 sec/mm2, respectively) diffusion-weighted (DW) imaging in the differentiation of true progression from pseudoprogression in glioblastoma treated with radiation therapy and concomitant temozolomide. Materials and Methods This retrospective study was approved by the institutional review board of Seoul National University Hospital, and informed consent requirement was waived. Thirty patients with histopathologically proved glioblastoma who had undergone concurrent chemotherapy and radiation therapy (CCRT) with temozolomide underwent diffusion-weighted MR imaging with b values of 1000 and 3000 sec/mm2, and corresponding ADC maps were calculated from entire newly developed or enlarged enhancing lesions after completion of CCRT. Histogram parameters of each ADC map between true progression (n = 15) and pseudoprogression (n = 15) groups were compared by using the unpaired Student t test. Receiver operating characteristic analysis was used to determine the best cutoff values for predictors in the differentiation of true progression from pseudoprogression. Results were validated in an independent test set of nine patients by using the best cutoff value to predict differentiation of true progression from pseudoprogression. The accuracy of the selected best cutoff value in the independent test set was then calculated. Results In terms of cumulative histograms, the fifth percentile of both ADC at b value of 1000 sec/mm2 (ADC1000) and the ADC at b value of 3000 sec/mm2 (ADC3000) were significantly lower in the true progression group than in the pseudoprogression group (P = .049 and P < .001, respectively). In contrast, neither the mean ADC1000 nor the mean ADC3000 was significantly different between the two groups. The diagnostic values of the parameters derived from ADC1000 and ADC3000 were compared, and a significant difference (0.224, P = .016) was found between the area under the receiver operating characteristic curve of the fifth percentile for ADC1000 and that for ADC3000. The accuracies were 66.7% (six of nine patients) and 88.9% (eight of nine patients) based on the fifth percentile of both ADC1000 and ADC3000 in the independent test set, respectively. Conclusion The fifth percentile of the cumulative ADC histogram obtained at a high b value was the most promising parameter in the differentiation of true progression from pseudoprogression of the newly developed or enlarged enhancing lesions after CCRT with temozolomide for glioblastoma treatment. © RSNA, 2013 Online supplemental material is available for this article.

Differentiation of True Progression from Pseudoprogression in Glioblastoma Treated with Radiation Therapy and Concomitant Temozolomide: Comparison Study of Standard and High-b-Value Diffusion-weighted Imaging

To explore the role of histogram analysis of apparent diffusion coefficient (ADC) maps obtained at standard- and high-b-value (1000 and 3000 sec/mm(2), respectively) diffusion-weighted (DW) imaging in the differentiation of true progression from pseudoprogression in glioblastoma treated with radiation therapy and concomitant temozolomide. This retrospective study was approved by the institutional review board of Seoul National University Hospital, and informed consent requirement was waived. Thirty patients with histopathologically proved glioblastoma who had undergone concurrent chemotherapy and radiation therapy (CCRT) with temozolomide underwent diffusion-weighted MR imaging with b values of 1000 and 3000 sec/mm(2), and corresponding ADC maps were calculated from entire newly developed or enlarged enhancing lesions after completion of CCRT. Histogram parameters of each ADC map between true progression (n = 15) and pseudoprogression (n = 15) groups were compared by using the unpaired Student t test. Receiver operating characteristic analysis was used to determine the best cutoff values for predictors in the differentiation of true progression from pseudoprogression. Results were validated in an independent test set of nine patients by using the best cutoff value to predict differentiation of true progression from pseudoprogression. The accuracy of the selected best cutoff value in the independent test set was then calculated. In terms of cumulative histograms, the fifth percentile of both ADC at b value of 1000 sec/mm(2) (ADC1000) and the ADC at b value of 3000 sec/mm(2) (ADC3000) were significantly lower in the true progression group than in the pseudoprogression group (P = .049 and P < .001, respectively). In contrast, neither the mean ADC1000 nor the mean ADC3000 was significantly different between the two groups. The diagnostic values of the parameters derived from ADC1000 and ADC3000 were compared, and a significant difference (0.224, P = .016) was found between the area under the receiver operating characteristic curve of the fifth percentile for ADC1000 and that for ADC3000. The accuracies were 66.7% (six of nine patients) and 88.9% (eight of nine patients) based on the fifth percentile of both ADC1000 and ADC3000 in the independent test set, respectively. The fifth percentile of the cumulative ADC histogram obtained at a high b value was the most promising parameter in the differentiation of true progression from pseudoprogression of the newly developed or enlarged enhancing lesions after CCRT with temozolomide for glioblastoma treatment. Online supplemental material is available for this article.