Dynamic Susceptibility Contrast-enhanced Research Articles

Differentiation Between High-Grade Glioma and Brain Metastasis Using Cerebral Perfusion-Related Parameters (Cerebral Blood Volume and Cerebral Blood Flow): A Systematic Review and Meta-Analysis of Perfusion-weighted MRI Techniques.

Distinguishing high-grade gliomas (HGGs) from brain metastases (BMs) using perfusion-weighted imaging (PWI) remains challenging. PWI offers quantitative measurements of cerebral blood flow (CBF) and cerebral blood volume (CBV), but optimal PWI parameters for differentiation are unclear. To compare CBF and CBV derived from PWIs in HGGs and BMs, and to identify the most effective PWI parameters and techniques for differentiation. Systematic review and meta-analysis. Twenty-four studies compared CBF and CBV between HGGs (n = 704) and BMs (n = 488). Arterial spin labeling (ASL), dynamic susceptibility contrast (DSC), dynamic contrast-enhanced (DCE), and dynamic susceptibility contrast-enhanced (DSCE) sequences at 1.5 T and 3.0 T. Following the PRISMA guidelines, four major databases were searched from 2000 to 2024 for studies evaluating CBF or CBV using PWI in HGGs and BMs. Standardized mean difference (SMD) with 95% CIs was used. Risk of bias (ROB) and publication bias were assessed, and I2 statistic was used to assess statistical heterogeneity. A P-value<0.05 was considered significant. HGGs showed a significant modest increase in CBF (SMD = 0.37, 95% CI: 0.05-0.69) and CBV (SMD = 0.26, 95% CI: 0.01-0.51) compared with BMs. Subgroup analysis based on region, sequence, ROB, and field strength for CBF (HGGs: 375 and BMs: 222) and CBV (HGGs: 493 and BMs: 378) values were conducted. ASL showed a considerable moderate increase (50% overlapping CI) in CBF for HGGs compared with BMs. However, no significant difference was found between ASL and DSC (P = 0.08). ASL-derived CBF may be more useful than DSC-derived CBF in differentiating HGGs from BMs. This suggests that ASL may be used as an alternative to DSC when contrast medium is contraindicated or when intravenous injection is not feasible. Stage 2.

Comparison of ASL and DSC perfusion methods in the evaluation of response to treatment in patients with a history of treatment for malignant brain tumor

ObjectivePerfusion MRI is of great benefit in the post-treatment evaluation of brain tumors. Interestingly, dynamic susceptibility contrast-enhanced (DSC) perfusion has taken its place in routine examination for this purpose. The use of arterial spin labeling (ASL), a perfusion technique that does not require exogenous contrast material injection, has gained popularity in recent years. The aim of the study was to compare two different perfusion techniques, ASL and DSC, using qualitative and quantitative measurements and to investigate the diagnostic effectiveness of both. The fact that the number of patients is higher than in studies conducted with 3D pseudo-continious ASL (pCASL), the study group is heterogeneous as it consists of patients with both metastases and glial tumors, the use of 3D Turbo Gradient Spin Echo (TGSE), and the inclusion of visual (qualitative) assessment make our study unique.MethodsNinety patients, who were treated for malignant brain tumor, were enrolled in the retrospective study. DSC Cerebral Blood Volume (CBV), Cerebral Blood Flow (CBF) and ASL CBF maps of each case were obtained. In qualitative analysis, the lesions of the cases were visually classified as treatment-related changes (TRC) and relapse/residual mass (RRT). In the quantitative analysis, three regions of interest (ROI) measurements were taken from each case. The average of these measurements was compared with the ROI taken from the contralateral white matter and normalized values (n) were obtained. These normalized values were compared across events.ResultsUncorrected DSC normalized CBV (nCBV), DSC normalized CBF (nCBF) and ASL nCBF values of RRT cases were higher than those of TRC cases (p < 0.001). DSC nCBV values were correlated with DSC nCBF (r: 0.94, p < 0.001) and correlated with ASL nCBF (r: 0.75, p < 0.001). Similarly, ASL nCBF was positively correlated with DSC nCBF (r: 0.79 p < 0.01). When the ROC curve parameters were evaluated, the cut-off values were determined as 1.211 for DSC nCBV (AUC: 0.95, 93% sensitivity, 82% specificity), 0.896 for DSC nCBF (AUC; 0.95, 93% sensitivity, 82% specificity), and 0.829 for ASL nCBF (AUC: 0.84, 78% sensitivity, 75% specificity). For qualitative evaluation (visual evaluation), inter-observer agreement was found to be good for ASL CBF (0.714), good for DSC CBF (0.790), and excellent for DSC CBV (0.822). Intra-observer agreement was also evaluated. For the first observer, good agreement was found in ASL CBF (0.626, 70% sensitive, 93% specific), in DSC CBF (0.713, 76% sensitive, 95% specific), and in DSC CBV (0.755, 87% sensitive - 88% specific). In the second observer, moderate agreement was found in ASL CBF (0.584, 61% sensitive, 97% specific) and DSC CBF (0.649, 65% sensitive, 100% specific), and excellent agreement in DSC CBV (0.800, 89% sensitive, 90% specific).ConclusionIt was observed that uncorrected DSC nCBV, DSC nCBF and ASL nCBF values were well correlated with each other. In qualitative evaluation, inter-observer and intra-observer agreement was higher in DSC CBV than DSC CBF and ASL CBF. In addition, DSC CBV is found more sensitive, ASL CBF and DSC CBF are found more specific for both observers. From a diagnostic perspective, all three parameters DSC CBV, DSC CBF and ASL CBF can be used, but it was observed that the highest rate belonged to DSC CBV.

Multiparametric analysis from dynamic susceptibility contrast-enhanced perfusion MRI to evaluate malignant brain tumors.

Dynamic susceptibility contrast-enhanced (DSC) MR perfusion is a valuable technique for distinguishing brain tumors. Diagnostic potential of measurable parameters derived from preload leakage-corrected-DSC-MRI remains somewhat underexplored. This study aimed to evaluate these parameters for differentiating primary CNS lymphoma (PCNSL), glioblastoma, and metastasis. Thirty-nine patients with pathologically proven PCNSL (n = 14), glioblastoma (n = 14), and metastasis (n = 11) were analyzed. Five DSC parameters-relative CBV (rCBV), percentage of signal recovery (PSR), downward slope (DS), upward slope (US), and first-pass slope ratio-were derived from tumor-enhancing areas. Diagnostic performance was assessed using receiver operating characteristic curve analysis. RCBV was higher in metastasis (4.58; interquartile range [IQR]: 2.54) and glioblastoma (3.98; IQR: 1.87), compared with PCNSL (1.46; IQR: 0.29; p = .00006 for both). rCBV better distinguished metastasis and glioblastoma from PCNSL, with an area under the curve (AUC) of 0.97 and 0.99, respectively. PSR was higher in PCNSL (88.11; IQR: 21.21) than metastases (58.30; IQR: 22.28; p = .0002), while glioblastoma (74.54; IQR: 21.23) presented almost significant trend-level differences compared to the others (p≈.05). AUCs were 0.79 (PCNSL vs. glioblastoma), 0.91 (PCNSL vs. metastasis), and 0.78 (glioblastoma vs. metastasis). DS and US parameters were statistically significant between glioblastoma (-109.92; IQR: 152.71 and 59.06; IQR: 52.87) and PCNSL (-47.36; IQR: 44.30 and 21.68; IQR: 16.85), presenting AUCs of 0.86 and 0.87. Metastasis and glioblastoma can be better differentiated from PCNSL through rCBV. PSR demonstrated higher differential performance compared to the other parameters and seemed useful, allowing a proper distinction among all, particularly between metastasis and glioblastoma, where rCBV failed. Finally, DS and US were only helpful in differentiating glioblastoma from PCNSL.

Conventional and Advanced Magnetic Resonance Imaging Assessment of Non-Enhancing Peritumoral Area in Brain Tumor.

The non-enhancing peritumoral area (NEPA) is defined as the hyperintense region in T2-weighted and fluid-attenuated inversion recovery (FLAIR) images surrounding a brain tumor. The NEPA corresponds to different pathological processes, including vasogenic edema and infiltrative edema. The analysis of the NEPA with conventional and advanced magnetic resonance imaging (MRI) was proposed in the differential diagnosis of solid brain tumors, showing higher accuracy than MRI evaluation of the enhancing part of the tumor. In particular, MRI assessment of the NEPA was demonstrated to be a promising tool for distinguishing high-grade gliomas from primary lymphoma and brain metastases. Additionally, the MRI characteristics of the NEPA were found to correlate with prognosis and treatment response. The purpose of this narrative review was to describe MRI features of the NEPA obtained with conventional and advanced MRI techniques to better understand their potential in identifying the different characteristics of high-grade gliomas, primary lymphoma and brain metastases and in predicting clinical outcome and response to surgery and chemo-irradiation. Diffusion and perfusion techniques, such as diffusion tensor imaging (DTI), diffusional kurtosis imaging (DKI), dynamic susceptibility contrast-enhanced (DSC) perfusion imaging, dynamic contrast-enhanced (DCE) perfusion imaging, arterial spin labeling (ASL), spectroscopy and amide proton transfer (APT), were the advanced MRI procedures we reviewed.

Monitoring Posterior Cerebral Perfusion Changes With Dynamic Susceptibility Contrast-Enhanced Perfusion MRI After Anterior Revascularization Surgery in Pediatric Moyamoya Disease.

To determine whether dynamic susceptibility contrast-enhanced (DSC) perfusion magnetic resonance imaging (MRI) can be used to evaluate posterior cerebral circulation in pediatric patients with moyamoya disease (MMD) who underwent anterior revascularization. This study retrospectively included 73 patients with MMD who underwent DSC perfusion MRI (age, 12.2 ± 6.1 years) between January 2016 and December 2020, owing to recent-onset clinical symptoms during the follow-up period after completion of anterior revascularization. DSC perfusion images were analyzed using a dedicated software package (NordicICE; Nordic NeuroLab) for the middle cerebral artery (MCA), posterior cerebral artery (PCA), and posterior border zone between the two regions (PCA-MCA). Patients were divided into two groups; the PCA stenosis group included 30 patients with newly confirmed PCA involvement, while the no PCA stenosis group included 43 patients without PCA involvement. The relationship between DSC perfusion parameters and PCA stenosis, as well as the performance of the parameters in discriminating between groups, were analyzed. In the PCA stenosis group, the mean follow-up duration was 5.3 years after anterior revascularization, and visual disturbances were a common symptom. Normalized cerebral blood volume was increased, and both the normalized time-to-peak (nTTP) and mean transit time values were significantly delayed in the PCA stenosis group compared with those in the no PCA stenosis group in the PCA and PCA-MCA border zones. TTPPCA (odds ratio [OR] = 6.745; 95% confidence interval [CI] = 2.665-17.074; P < 0.001) and CBVPCA-MCA (OR = 1.567; 95% CI = 1.021-2.406; P = 0.040) were independently associated with PCA stenosis. TTPPCA showed the highest receiver operating characteristic curve area in discriminating for PCA stenosis (0.895; 95% CI = 0.803-0.986). nTTP can be used to effectively diagnose PCA stenosis. Therefore, DSC perfusion MRI may be a valuable tool for monitoring PCA stenosis in patients with MMD.

Association of Relative Cerebral Blood Volume from Dynamic Susceptibility Contrast-Enhanced Perfusion MR with HER2 Status in Breast Cancer Brain Metastases

With the development of HER2-directed therapies, identifying non-invasive imaging biomarkers of HER2 expression in breast cancer brain metastases has become increasingly important. The purpose of this study was to investigate whether relative cerebral blood volume (rCBV) from dynamic susceptibility contrast-enhanced (DSC) perfusion MR could help identify the HER2 status of breast cancer brain metastases. With IRB approval for this HIPAA-compliant cross-sectional study and a waiver of informed consent, we queried our institution's electronic medical record to derive a cohort of 14 histologically proven breast cancer brain metastases with preoperative DSC perfusion MR and HER2 analyses of the resected/biopsied brain specimens from 2011-2021. The rCBV of the lesions was measured and compared using Mann-Whitney tests. Receiver operating characteristic analyses were performed to evaluate the performance of rCBV in identifying HER2 status. The study cohort was comprised of 14 women with a mean age of 56 years (range: 32-81 years) with a total of 14 distinct lesions. The rCBV of HER2-positive breast cancer brain metastases was significantly greater than the rCBV of HER2-negative lesions (8.02 vs 3.97, U=48.00, p=0.001). rCBV differentiated HER2-positive lesions from HER2-negative lesions with an area under the curve of 0.98 (standard error=0.032, p<0.001). The accuracy-maximizing rCBV threshold (4.8) was associated with an accuracy of 93% (13/14), a sensitivity of 100% (7/7), and a specificity of 86% (6/7). rCBV may assist in identifying the HER2 status of breast cancer brain metastases, if validated in a large prospective trial.

Diffusion kurtosis imaging combined with dynamic susceptibility contrast-enhanced MRI in differentiating high-grade glioma recurrence from pseudoprogression

ObjectivesTo compare the added value of diffusion kurtosis imaging (DKI) with the combination of dynamic susceptibility contrast-enhanced (DSC) MRI in differentiating glioma recurrence from pseudoprogression. MethodsThirty-four patients with high-grade gliomas developing new and/or increasing enhanced lesions within six months after surgery and chemoradiotherapy were retrospectively analyzed. All patients were pathologically confirmed to have recurrent glioma (n = 22) or pseudoprogression (n = 12). The DKI and DSC MRI parameters were calculated based on the enhanced lesions on contrast-enhanced T1WI. ROC analysis was performed on significant variables to determine their diagnostic performance. Multivariate logistic regression was used to determine the best prediction model for discrimination. ResultsThe relative mean kurtosis (rMK), relative axial kurtosis (rKa), relative cerebral blood volume (rCBV), and relative mean transit time (rMTT) of glioma recurrence were higher than those of pseudoprogression (all, P < 0.05). The AUCs and diagnostic accuracy were 0.879 and 82.35% for rMK, 0.723 and 70.59% for rKa, 0.890 and 82.35% for rCBV, 0.765 and 73.53% for rMTT, respectively. A multivariate logistic regression model showed a significant contribution of rMK (P = 0.006) and rCBV (P = 0.009) as independent imaging classifiers for discrimination. The combined use of rMK and rCBV improved the AUC to 0.924 (P < 0.001) and the diagnostic accuracy to 88.24%. ConclusionDKI may be a valuable non-invasive tool in differentiating glioma recurrence from pseudoprogression, and its use in combination with DSC MRI can improve diagnostic performance in assessing treatment response compared with either technique alone.

Quantification of tumor microenvironment acidity in glioblastoma using principal component analysis of dynamic susceptibility contrast enhanced MR imaging

Glioblastoma (GBM) has high metabolic demands, which can lead to acidification of the tumor microenvironment. We hypothesize that a machine learning model built on temporal principal component analysis (PCA) of dynamic susceptibility contrast-enhanced (DSC) perfusion MRI can be used to estimate tumor acidity in GBM, as estimated by pH-sensitive amine chemical exchange saturation transfer echo-planar imaging (CEST-EPI). We analyzed 78 MRI scans in 32 treatment naïve and post-treatment GBM patients. All patients were imaged with DSC-MRI, and pH-weighting that was quantified from CEST-EPI estimation of the magnetization transfer ratio asymmetry (MTRasym) at 3 ppm. Enhancing tumor (ET), non-enhancing core (NC), and peritumoral T2 hyperintensity (namely, edema, ED) were used to extract principal components (PCs) and to build support vector machines regression (SVR) models to predict MTRasym values using PCs. Our predicted map correlated with MTRasym values with Spearman’s r equal to 0.66, 0.47, 0.67, 0.71, in NC, ET, ED, and overall, respectively (p < 0.006). The results of this study demonstrates that PCA analysis of DSC imaging data can provide information about tumor pH in GBM patients, with the strongest association within the peritumoral regions.

Non-Invasive Evaluation of Cerebral Microvasculature Using Pre-Clinical MRI: Principles, Advantages and Limitations.

Alterations to the cerebral microcirculation have been recognized to play a crucial role in the development of neurodegenerative disorders. However, the exact role of the microvascular alterations in the pathophysiological mechanisms often remains poorly understood. The early detection of changes in microcirculation and cerebral blood flow (CBF) can be used to get a better understanding of underlying disease mechanisms. This could be an important step towards the development of new treatment approaches. Animal models allow for the study of the disease mechanism at several stages of development, before the onset of clinical symptoms, and the verification with invasive imaging techniques. Specifically, pre-clinical magnetic resonance imaging (MRI) is an important tool for the development and validation of MRI sequences under clinically relevant conditions. This article reviews MRI strategies providing indirect non-invasive measurements of microvascular changes in the rodent brain that can be used for early detection and characterization of neurodegenerative disorders. The perfusion MRI techniques: Dynamic Contrast Enhanced (DCE), Dynamic Susceptibility Contrast Enhanced (DSC) and Arterial Spin Labeling (ASL), will be discussed, followed by less established imaging strategies used to analyze the cerebral microcirculation: Intravoxel Incoherent Motion (IVIM), Vascular Space Occupancy (VASO), Steady-State Susceptibility Contrast (SSC), Vessel size imaging, SAGE-based DSC, Phase Contrast Flow (PC) Quantitative Susceptibility Mapping (QSM) and quantitative Blood-Oxygenation-Level-Dependent (qBOLD). We will emphasize the advantages and limitations of each strategy, in particular on applications for high-field MRI in the rodent’s brain.

Prediction of IDH Mutation Status in High-grade Gliomas Using DWI and High T1-weight DSC-MRI

We aimed to evaluate the diagnostic performance of diffusion-weighted imaging (DWI) and dynamic susceptibility contrast-enhanced (DSC) magnetic resonance imaging (MRI) parameters in the noninvasive prediction of the isocitrate dehydrogenase (IDH) mutation status in high-grade gliomas (HGGs). A total of 58 patients with histopathologically proved HGGs were included in this retrospective study. All patients underwent multiparametric MRI on 3-T, including DSC-MRI and DWI before surgery. The mean apparent diffusion coefficient (ADC), relative maximum cerebral blood volume (rCBV), and percentage signal recovery (PSR) of the tumor core were measured and compared depending on the IDH mutation status and tumor grade. The Mann-Whitney U test was used to detect statistically significant differences in parameters between IDH-mutant-type (IDH-m-type) and IDH-wild-type (IDH-w-type) HGGs. Receiver operating characteristic curve (ROC) analysis was performed to evaluate the diagnostic performance. The rCBV was significantly higher, and the PSR value was significantly lower in IDH-w-type tumors than in the IDH-m group (p = 0.002 and <0.001, respectively).The ADC value in IDH-w-type tumors was significantly lower compared with the one in IDH-m types (p = 0.023), but remarkable overlaps were found between the groups. The PSR showed the best diagnostic performance with an AUC of 0.938 and with an accuracy rate of 0.87 at the optimal cutoff value of 86.85. The combination of the PSR and the rCBV for the identification of the IDH mutation status increased the discrimination ability at the AUC level of 0.955. In terms of each tumor grade, the PSR and rCBV showed significant differences between the IDH-m and IDH-w groups (p ≤0.001). The rCBV and PSR from DSC-MRI may be feasible noninvasive imaging parameters for predicting the IDH mutation status in HGGs. The standardization of the imaging protocol is indispensable to the utility of DSC perfusion MRI in wider clinical usage.

Brain tumor segmentation using 3D Mask R-CNN for dynamic susceptibility contrast enhanced perfusion imaging

The segmentation of neoplasms is an important part of radiotherapy treatment planning, monitoring disease progression, and predicting patient outcome. In the brain, functional magnetic resonance imaging (MRI) like dynamic susceptibility contrast enhanced (DSCE) or T1-weighted dynamic contrast enhanced (DCE) perfusion MRI are important tools for diagnosis. They play a crucial role in providing pre-operative assessment of tumor histology, grading, and biopsy guidance. However, the manual contouring of these neoplasms is tedious, expensive, time-consuming, and vulnerable to inter-observer variability. In this work, we propose a 3D mask region-based convolutional neural network (R-CNN) method to automatically segment brain tumors in DSCE MRI perfusion images. As our goal is to simultaneously localize and segment the tumor, our training process contained both a region-of-interest (ROI) localization and regression with voxel-wise segmentation. The combination of classification loss, ROI location and size regression loss, and segmentation loss were used to supervise the proposed network. We retrospectively investigated 21 patients’ perfusion images, with between 50 and 70 perfusion time point volumes, a total of 1260 3D volumes. Tumor contours were automatically segmented by our proposed method and compared against other state-of-the-art methods and those delineated by physicians as the ground truth. The results of our method demonstrated good agreement with the ground truth contours. The average DSC, precision, recall, Hausdorff distance, mean surface distance (MSD), root MSD, and center of mass distance were 0.90 ± 0.04, 0.91 ± 0.04, 0.90 ± 0.06, 7.16 ± 5.78 mm, 0.45 ± 0.34 mm, 1.03 ± 0.72 mm, and 0.86 ± 0.91 mm, respectively. These results support the feasibility of our method in accurately localizing and segmenting brain tumors in DSCE perfusion MRI. Our 3D Mask R-CNN segmentation method in DSCE perfusion imaging has great promise for future clinical use.

99mTc]-Bis-Methionine-DTPA Single-Photon Emission Computed Tomography Impacting Glioma Management: A Sensitive Indicator for Postsurgical/Chemoradiotherapy Response Assessment.

Background: The present study evaluated the prognostic value of [99mTc]MDM (bis-methionine-DTPA) follow-up single-photon emission computed tomography (SPECT) imaging for response assessment to chemoradiotherapy in glioma postoperatively. Materials and Methods: One hundred fourteen glioma patients (80 M:34 F) were followed postoperatively by sequential [99mTc]MDM SPECT, dynamic susceptibility contrast-enhanced (DSCE)-MRI, and magnetic resonance spectroscopy (MRS) at baseline, 6, 12, and 22.5 months postchemoradiotherapy. The quantitative imaging results and the clinical outcome were used for response assessment and for the final diagnosis. The quantitative parameter of [99mTc]MDM SPECT were also used for survival analysis. Results: A significantly (p = 0.001) lower target to nontarget (T/NT) ratio was observed in responders than in nonresponders. The sensitivity and specificity of [99mTc]MDM-SPECT for identifying tumor recurrence from radiation necrosis at a cutoff ratio of 1.90 were estimated at 97.9% and 92%. Whereas, the sensitivity and specificity of DSCE-MRI with the normalized cerebral blood volume (nCBV) cutoff of 3.32 for this differentiation was found to be 84.6% and 93.0%. MRS intensity ratios of Cho/NAA and Cho/Cr provided comparatively lower sensitivity of 81.0% and 85.3% and specificity of 73.0% and 73.7%. T/NT ratios correlated with nCBV (r = 0.775, p < 0.001) and to a moderate extent with Cho/NAA ratios (r = 0.467, p = 0.001). [99mTc]MDM SPECT and DSCE-MRI provided comparable results for predicting response assessment to chemoradiotherapy. There was a final diagnosis in 72 patients, of which 47 cases were tumor recurrence and 25 were radiation necrosis. The Kaplan-Meier analysis indicated that patients with T/NT ratio <1.9 showed prolonged survival (53.8 months) as compared (37.2 months) with those who demonstrated T/NT ratio >1.9 (p = 0.0001). Conclusion: Thus, this low-cost SPECT technique in combination with DSCE-MRI can be used accurately for mapping the disease activity, response assessment, and survival in glioma. [99mTc]MDM SPECT and DSCE-MRI had the same diagnostic efficacy to detect recurrent/residual tumor and radiation necrosis while MRS was inferior to both the techniques.

Differentiation of progressive disease from pseudoprogression using 3D PCASL and DSC perfusion MRI in patients with glioblastoma.

To use 3D pseudocontinuous arterial spin labeling (3D PCASL) and dynamic susceptibility contrast-enhanced (DSC) perfusion MRI to differentiate progressive disease from pseudoprogression in patients with glioblastoma (GBM). Thirty-two patients with GBM who developed progressively enhancing lesions within the radiation field following resection and chemoradiation were included in this retrospective, single-institution study. The updated modified RANO criteria were used to establish progressive disease or pseudoprogression. Following 3D PCASL and DSC MR imaging, perfusion parameter estimates of cerebral blood flow (ASL-nCBF and DSC-nrCBF) and cerebral blood volume (DSC-nrCBV) were calculated. Additionally, contrast enhanced volumes were measured. Mann-Whitney U tests were used to compare groups. Linear discriminant analysis (LDA) and area under receiver operator characteristic curve (AUC) analyses were used to evaluate performance of each perfusion parameter and to determine optimal cut-off points. All perfusion parameter measurements were higher in patients with progressive disease (mean, 95% CI ASL-nCBF 2.48, [2.03, 2.93]; DSC-nrCBF = 2.27, [1.85, 2.69]; DSC-nrCBV = 3.51, [2.37, 4.66]) compared to pseudoprogression (mean, 95% CI ASL-nCBF 0.99, [0.47, 1.52]; DSC-nrCBF = 1.05, [0.36, 1.74]; DSC-nCBV = 1.19, [0.34, 2.05]), and findings were significant at the p < 0.0125 level (p = 0.001, 0.003, 0.002; effect size: Cohen's d = 1.48, 1.27, and 0.92). Contrast enhanced volumes were not significantly different between groups (p > 0.447). All perfusion parameters demonstrated high AUC (0.954 for ASL-nCBF, 0.867 for DSC-nrCBF, and 0.891 for DSC-nrCBV), however, ASL-nCBF demonstrated the highest AUC and misclassified the fewest cases (N = 6). Lesions correctly classified by ASL but misclassified by DSC were located along the skull base or adjacent to large resection cavities with residual blood products, at areas of increased susceptibility. Both 3D PCASL and DSC perfusion MRI techniques have nearly equivalent performance for the differentiation of progressive disease from pseudoprogression in patients with GBM. However, 3D PCASL is less sensitive to susceptibility artifact and may allow for improved classification in select cases.

Prognostication of anaplastic astrocytoma patients: application of contrast leakage information of dynamic susceptibility contrast-enhanced MRI and dynamic contrast-enhanced MRI.

To examine the applicability of contrast leakage information from dynamic susceptibility contrast-enhanced (DSC) MRI and dynamic contrast-enhanced (DCE) MRI to determine which one is the most valuable surrogate imaging biomarker for predicting disease progression in anaplastic astrocytoma (AA) patients. This study was approved by the institutional review board (IRB), which waived informed consent. A total of seventy-three AA patients who had undergone preoperative DCE and DSC MRI and received standard treatment, including partial resection or biopsy followed by radiation therapy, were included in this retrospective study. Based on Response Assessment in Neuro-Oncology (RANO), patients were sorted into progression (n = 21) and non-progression (n = 52) groups. Tumor boundaries were defined as high-signal intensity (SI) lesions on fluid-attenuated inversion recovery (FLAIR) imaging, where we analyzed mean pharmacokinetic parameters (Ktrans, Vp, and Ve) from DCE MRI and contrast leakage information (mean extraction fraction (EF)) from DSC MRI. Mean Ve and mean EF were significantly higher in patients with progression-free survival (PFS) < 18 months than in those with PFS ≥ 18 months. For distinguishing the group with PFS < 18 months, AUC values were calculated using the mean Ve value (AUC = 0.716). The Kaplan-Meier survival analysis revealed that mean Ve value was significantly correlated with PFS. In Cox proportional-hazards regression, only the mean Ve value was found to be significantly associated with PFS. We found that the mean Ve value based on high-SI tumor lesions on FLAIR imaging was capable of predicting outcomes of AA patients as a potential surrogate imaging biomarker. • Mean Ve(2.152 ± 1.857 vs. 1.173 ± 1.408) was significantly higher in anaplastic astrocytoma patients with PFS < 18 months that in those with PFS ≥ 18 months (p = 0.02). • Cox proportional-hazards regression showed that only mean Ve(p = 0.034) was significantly associated with PFS, regardless of IDH mutation status, in anaplastic astrocytoma patients.

Comparing amide proton transfer imaging with dynamic susceptibility contrast-enhanced perfusion in predicting histological grades of gliomas: a meta-analysis.

Background As a subtype of chemical exchange saturation transfer imaging without contrast agent administration, amide proton transfer (APT) imaging has demonstrated the potential for differentiating the histologic grades of gliomas. Dynamic susceptibility contrast-enhanced perfusion, a perfusion-weighted imaging technique, is a well-established technique in grading gliomas. Purpose To compare the ability of amide proton transfer and dynamic susceptibility contrast-enhanced imaging for predicting the grades of gliomas. Material and Methods A comprehensive literature search was performed independently by two observers to identify articles about the diagnostic performance of amide proton transfer and dynamic susceptibility contrast-enhanced perfusion in predicting the grade of gliomas. Summary estimates of diagnostic accuracy were obtained by using a random-effects model. Results Of 179 studies identified, 23 studies were included the analysis. Eight studies evaluated amide proton transfer and 16 studies evaluated dynamic susceptibility contrast-enhanced perfusion with the parameter rCBV. The pooled sensitivities and specificities of each study’s best performing parameter were 88% (95% confidence interval [CI] 74–95) and 89% (95% CI 78–95) for amide proton transfer, and 95% (95% CI 87–98), 88% (95% CI 81–93) for perfusion-weighted imaging–dynamic susceptibility contrast-enhanced perfusion, respectively. The pooled sensitivities and specificities for grading gliomas using the two most commonly evaluated parameters, were 92% (95% CI 80–97) and 90% (95% CI 75–96) for APTmax, and 97% (95% CI 91–99) and 87% (95% CI 80–92) for rCBVmax, respectively. Conclusion Considering the similar performance of APT and dynamic susceptibility contrast-enhanced (DSC) in predicting glioma grade, the former method appears preferable since it needs no contrast agent.

Sex-specific differences in white matter microvascular integrity after ischaemic stroke

Background and purposeFunctional outcomes after ischaemic stroke are worse in women, despite adjusting for differences in comorbidities and treatment approaches. White matter microvascular integrity represents one risk factor for poor...

Combination value of diffusion-weighted imaging and dynamic susceptibility contrast-enhanced MRI in astrocytoma grading and correlation with GFAP, Topoisomerase IIα and MGMT.

The present study aimed to investigate the value of diffusion-weighted imaging (DWI) combined with dynamic susceptibility contrast-enhanced (DSC) magnetic resonance imaging (MRI) scans in astrocytoma grading, and correlated MRI scan parameters of values of apparent diffusion coefficient (ADC) and relative cereberal blood volume (rCBV) with the immunohistochemical (IHC) indices of glial fibrillary acidic protein (GFAP), topoisomerase IIα (Topo IIα) and O 6-methylguanine-DNA methyltransferase (MGMT). A total of 123 patients with pathologically confirmed astrocytomas of differing grades underwent DWI and DSC scans. The values of the ADC and relative cerebral blood volume rCBV were compared with the grade II–IV astrocytomas. Receiver operating characteristic curves were used to compare astrocytoma grading efficiency of ADC, rCBV and the combination of the two values. The parameters of ADC and rCBV with GFAP, Topo IIα and MGMT indices were then correlated. The differences in ADC values were significant between the grades II, III and IV astrocytomas, and the rCBV values for grades II, III and IV were also significant. The combination of DWI and DSC demonstrated the highest values for area under curve in identifying grades II and III, and identifying grades III and IV, respectively. GFAP displayed a positive correlation with ADC and a negative correlation with rCBV. Topo IIα exhibited a negative correlation with ADC, and a positive correlation with rCBV. No correlation was observed between MGMT and ADC or rCBV. The combined application of DWI and DSC may increase astrocytoma grading accuracy. Values of ADC and rCBV exhibit certain correlations with IHC indices, and may predict degree of malignancy of astrocytoma.

Machine-learning based classification of glioblastoma using delta-radiomic features derived from dynamic susceptibility contrast enhanced magnetic resonance images: Introduction.

Glioblastoma is the most aggressive brain tumor with poor prognosis. The purpose of this study is to improve the tissue characterization of these highly heterogeneous tumors using delta-radiomic features of images from dynamic susceptibility contrast enhanced (DSC) magnetic resonance imaging (MRI). Twenty-five patients with histopathologically confirmed to be 13 high-grade (HG) and 12 low-grade (LG) gliomas who underwent the standard brain tumor MRI protocol, including DSC MRI, were included. Tumor regions on all DSC MRI images were registered to and contoured in T2-weighted fluid-attenuated inversion recovery (FLAIR) images. These contours and its contralateral regions of the normal tissue were used to extract delta-radiomic features before applying feature selection. The most informative and non-redundant features were selected to train a random forest to differentiate HG and LG gliomas. Then a leave-one-out cross-validation random forest was applied to classify these tumors for grading. Finally, a majority-voting method was applied to reduce binarization bias and to combine the results of various feature lists. Analysis of the predictions showed that the reported method consistently predicted the tumor grade of 24 out of 25 patients correctly (0.96). Finally, the mean prediction accuracy was 0.950±0.091 for HG and 0.850±0.255 for LG. The area under the receiver operating characteristic curve (AUC) was 0.94. This study shows that delta-radiomic features derived from DSC MRI data can be used to characterize and determine the tumor grades. The radiomic features from DSC MRI may be used to elucidate the underlying tumor biology and response to therapy.

Differentiation of Recurrent/Residual Glioma From Radiation Necrosis Using Semi Quantitative 99mTc MDM (Bis-Methionine-DTPA) Brain SPECT/CT and Dynamic Susceptibility Contrast-Enhanced MR Perfusion: A Comparative Study.

In this study, Tc MDM (bis-methionine-DTPA) SPECT was used for the detection and differentiation of recurrent/residual glioma from radiation necrosis and the results were compared with dynamic susceptibility contrast-enhanced (DSCE)-MRI and clinical findings. Twenty-eight patients (18 men and 10 women; mean ± SD age, 41.4 ± 15.03 years) with histologically proven glioma (grade IV, 14; grade III, 7; grade II, 7) who were planned for postsurgical standard radio/chemo therapy were recruited prospectively. All the patients underwent technetium Tc MDM SPECT/CT and DSCE-MRI imaging at 6 months after surgery/radio-chemotherapy, 9 of 28 patients also underwent SPECT imaging at 1 to 2 weeks after surgery. Tc MDM SPECT/CT analysis demonstrated significantly higher target to nontarget (T/NT) ratio of the radiotracer in tumor recurrence than in radiation necrosis (3.59 ± 1.70 vs 1.16 ± 0.42). Likewise, the normalized cerebral blood volume (nCBV) values in patients with tumor recurrence were also significantly higher than in radiation necrosis (5.16 ± 2.30 vs 1.63 ± 0.94). A positive correlation (rho = 0.823, P < 0.0001) between T/NT ratios and nCBV was observed. The cutoff T/NT ratios and nCBV values estimated by receiver operating characteristic analysis were greater than 1.50 (area under the curve, 0.944 ± 0.34) and greater than 2.12 (area under the curve, 0.931 ± 0.39), respectively. Combining the results of Tc MDM SPECT/CT, DSCE-MRI, and clinical findings, diagnosis of recurrent/residual glioma or radiation necrosis was made in 18 and 10 patients, respectively. Sensitivity and specificity of 2 techniques were comparable, that is, 92.0%: 78.6% for MDM SPECT/CT and of 92.0%: 71.4% for DSCE-MRI, respectively. Thus, combining MDM SPECT with DSCE MRI may provide an accurate method for differentiation of tumor recurrence from radiation-induced necrosis in glioma patients.

Contrast-Enhanced Perfusion MR Imaging to Differentiate Between Recurrent/Residual Brain Neoplasms and Radiation Necrosis

Purpose:To determine the value of dynamic susceptibility contrast enhanced (DSC) MRI (magnetic resonance imaging) perfusion in the characterization of newly developed/enlarging lesions within irradiated regions after treatment of brain tumors.Methods:This prospective cross-sectional study covered 23 patients, 12 females and 11 males. All cases initially presented with histologically proven malignant brain tumors and underwent surgical intervention followed by radiotherapy (+/- chemotherapy). On follow up imaging, they presented with newly developed/progressively enhancing mass lesions at the sites of the primary tumors. All patients then underwent conventional MRI, DSC MRI perfusion and MR spectroscopy.Results:In our study, we found DSC MR perfusion to be a useful non-invasive method for differentiating recurrent brain tumors from radiation necrosis. This approach allows hemodynamic measurements to be obtained within the brain as the relative cerebral blood volume (rCBV) to complement the anatomic information obtained with conventional contrast enhanced MR imaging. The sensitivity and specificity of DSC MR perfusion for differentiation were found to be 77.8% and 80.0%, respectively.Conclusion:DSC MR perfusion is a promising technique in differentiating recurrent brain tumors from radiation necrosis as it has acceptable spatial resolution and can be routinely performed in the same settings after conventional MRI.