CBV Values Research Articles

Prediction of PD-L1 and Ki-67 status in primary central nervous system diffuse large B-cell lymphoma by diffusion and perfusion MRI: a preliminary study

ObjectiveTo assess whether diffusion and perfusion MRI derived parameters could non-invasively predict PD-L1 and Ki-67 status in primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL).MethodsWe retrospectively analyzed DWI, DSC-PWI, and morphological MRI (mMRI) in 88 patients with PCNS-DLBCL. The mMRI features were compared using chi-square tests or Fisher exact test. Minimum ADC (ADCmin), mean ADC(ADCmean), relative minimum ADC (rADCmin), relative mean ADC (rADCmean), and relative maximum CBV (rCBVmax) values were compared in PCNS-DLBCL with different molecular status by using the Mann-Whitney U test. The diagnostic performances were evaluated by receiver operating characteristic curves.ResultsPCNS-DLBCL with high PD-L1 expression demonstrated a significantly higher ADCmin value than those with low PD-L1. The ADCmean and rADCmean values were significantly lower in PCNS-DLBCL with high Ki-67 status compared with those in low Ki-67 status. Other ADC, CBV parameters, and mMRI features did not show any association with these molecular statuses The diagnostic efficacy of ADC values in assessing PD-L1 and Ki-67 status was relatively low, with area under the curves (AUCs) values less than 0.7.ConclusionsDWI-derived ADC values can provide some relevant information about PD-L1 and Ki-67 status in PCNS-DLBCL, but may not be sufficient to predict their expression due to the rather low diagnostic performance.

Abstract 129: An Automated Perfusion Collateral Score as a Tool to Predict Inter-Hospital Infarct Growth and Functional Outcome

Background: The accuracy of infarct growth prediction based on collateral scores, assessed on CT perfusion (CTP) and CT angiography, has been modest. We aimed to investigate the accuracy of infarct growth prediction using a novel collateral score based on two CTP parameters. Methods: Patients were included from CRISP2, a multi-center prospective cohort study of stroke patients with an anterior circulation large vessel occlusion who are transferred from a primary stroke center (PSC) to a comprehensive stroke center (CSC). CTP was performed at the PSC, and MRI was performed immediately after arrival at the CSC. The inter-hospital infarct growth rate was calculated as the difference between the co-registered infarct volumes on MRI and CTP divided by the time interval between the scans, with fast inter-hospital growth ≥ 5ml/h. The hypoperfusion intensity ratio (HIR) was defined as the ratio of the volumes of Tmax >6s and Tmax >10s, and the CBV index as the ratio of mean CBV values within the Tmax >6s volume and the mean CBV in normal brain regions. An automated collateral score, based on the HIR and CBV index, was calculated from the CTP images at the PSC ( Fig 1A ). Results: Of 183 patients who were included, 111 (61%) were classified as having good collaterals and 72 (39%) as poor. Patients with poor collaterals experienced more rapid early infarct growth (median 2.19 ml/h IQR [0.32, 5.46] vs 7.92 [4.23, 16.23]; p-value <0.001) and had worse 90-day functional outcomes (p=0.01). The combined collateral score, based on both HIR and CBVindex, showed a trend towards better prediction of fast infarct growth compared to HIR alone (HIR ≥ 0.40 = poor collaterals) and CBV alone (CBVindex < 0.85 = poor collaterals) ( Fig 1B ). Conclusion: A perfusion collateral score, based on HIR and CBV index, is strongly associated with inter-hospital infarct growth rate and functional outcome. This automated tool can aid in patient selection for (neuroprotective) treatment strategies and transfer decisions.

A retrospective study of non-equidistant interstitial brain CT perfusion scanning and prediction of time to peak

BackgroundEexploring the limits of CT cranial perfusion scan acquisition intervals and predicting time to peak. MethodsA retrospective analysis was conducted on 45 patients with suspected stroke who underwent brain CTP scans. Different sampling intervals were set based on the TDC. The patients were divided into four groups: Group 1 underwent continuous scanning with a uniform interval of 1.5 s; Group 2 had a uniform interval of 3 s; Group 3 had a 1.5-s interval between arterial and venous peak vertices with 1 point retained before and after the peak for 1.5 s and with a remaining acquisition interval of 4.5 s; and Group 4 had a uniform interval of 4.5 s. Statistical analysis was performed on the perfusion parameters of each group. Additionally, in 286 patients who underwent head and neck CTA examinations, the peak time of contrast medium was recorded, and the peak time was predicted based on factors such as age, height, weight, heart rate, systolic blood pressure, diastolic blood pressure, triglycerides, and total cholesterol. The results compared with Group 1 and Group 2, as well as Group 1 and Group 3, the P values of CBF, CBV, MTT, and Tmax in the left and right cerebral hemispheres of healthy subjects and in the infarct and noninfarct areas of patients were all >0.05. A comparison between Group 1 and Group 4 showed that right cerebral hemisphere CBF and CBV, left cerebral hemisphere CBF, CBV, and Tmax, infarct area CBV and Tmax, and noninfarct area CBF, CBV, and MTT had P values > 0.05, while other groups all had P values < 0.05. Bland‒Altman analysis showed that the perfusion parameters in Group 1 were consistent with those in Group 2, and those in Group 1 were consistent with those in Group 3. The radiation doses in the second and third groups were lower, and the dose in the third group was lower than that in the second group. ConclusionContinuous acquisition between the peak points of the arterial and venous phases, with 1 point reserved before and after the peak and a 4.5-s interval for the rest, represents the maximum time interval for CTP scanning and can effectively reduce the radiation dose. The formula Tmax (s) = 0.290 × height (cm) − 0.226 × heart rate (times/min) + 0.216 × age (years) − 1.901 × triglycerides (mmol/L) − 0.061 × systolic blood pressure (mmHg) − 7.216 (R2 = 0.449, F = 17.905, P < 0.01) was established for predicting time to peak enhancement.

NIMG-27. GLIOBLASTOMA IN THE MAKING? ADVANCED IMAGING TELLS "MOLECULAR GLIOBLASTOMA" APART FROM ASTROCYTOMA

Abstract The fifth WHO classification of tumors of the CNS allows the diagnosis of glioblastoma using specific molecular markers, even if the classical histological criteria (necrosis and neoangiogenesis) are not fulfilled. Since such cases also tend to lack blood-brain barrier disruption and necrosis on conventional imaging, these can be mistaken for low-grade astrocytomas. We investigated the potential of advanced imaging to capture tumor biology and thus reliably distinguish between those entities already preoperatively. Multimodal preoperative 3T-MRI scans were collected from 147 glioblastoma, 4 astrocytomas grade 4, 7 “Molecular glioblastoma” (molGBM) grade 4, 9 astrocytomas grade 2, and 12 astrocytomas grade 3. From AI-based multi-compartimental tumor segmentations, advanced imaging metrics from perfusion- and diffusion-imaging were automatically extracted. Two-sample t-test and one-way ANOVA analysis was performed to test for significant differences between apparent diffusion coefficient (ADC) and relative cerebral blood volume (rCBV). Interestingly, rCBV (signifying neoangiogenesis) was significantly higher in molGBM as opposed to astrocytomas for the 5th percentile as well as for mean and median values (p &amp;lt; 0.05). ADC values were consequently lower (indicating higher cellularity) in molGBM than in astrocytomas grade 2 and 3 in the 95th percentile (p &amp;lt; 0.05). Although no molGBM showed contrast-enhancement initially, one untreated case showed a flaccid barrier disruption at 30d follow-up. Interestingly, the molecular imaging at the earlier timepoint showed significantly higher CBV values in the non-enhancing tumor than common glioblastoma and astrocytoma grade 4 (p = 0.013, ANOVA), which indicates highly active tumor portions. Perhaps it is precisely these areas that are on the verge of barrier disruption. Our results support the hypothesis that molGBM are truly early glioblastomas. Better understanding the molecular mechanisms involved in the transition to “classical” glioblastoma promises to provide important insight into tumor biology and potential therapeutic targets.

Imaging the WHO 2021 Brain Tumor Classification: Fully Automated Analysis of Imaging Features of Newly Diagnosed Gliomas.

The fifth version of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) in 2021 brought substantial changes. Driven by the enhanced implementation of molecular characterization, some diagnoses were adapted while others were newly introduced. How these changes are reflected in imaging features remains scarcely investigated. We retrospectively analyzed 226 treatment-naive primary brain tumor patients from our institution who received extensive molecular characterization by epigenome-wide methylation microarray and were diagnosed according to the 2021 WHO brain tumor classification. From multimodal preoperative 3T MRI scans, we extracted imaging metrics via a fully automated, AI-based image segmentation and processing pipeline. Subsequently, we examined differences in imaging features between the three main glioma entities (glioblastoma, astrocytoma, and oligodendroglioma) and particularly investigated new entities such as astrocytoma, WHO grade 4. Our results confirm prior studies that found significantly higher median CBV (p = 0.00003, ANOVA) and lower median ADC in contrast-enhancing areas of glioblastomas, compared to astrocytomas and oligodendrogliomas (p = 0.41333, ANOVA). Interestingly, molecularly defined glioblastoma, which usually does not contain contrast-enhancing areas, also shows significantly higher CBV values in the non-enhancing tumor than common glioblastoma and astrocytoma grade 4 (p = 0.01309, ANOVA). This work provides extensive insights into the imaging features of gliomas in light of the new 2021 WHO CNS tumor classification. Advanced imaging shows promise in visualizing tumor biology and improving the diagnosis of brain tumor patients.

Diffuse Large B-Cell Epstein-Barr Virus-Positive Primary CNS Lymphoma in Non-AIDS Patients: High Diagnostic Accuracy of DSC Perfusion Metrics.

Immunodeficiency-associated CNS lymphoma may occur in different clinical scenarios beyond AIDS. This subtype of CNS lymphoma is diffuse large B-cell and Epstein-Barr virus-positive. Its accurate presurgical diagnosis is often unfeasible because it appears as ring-enhancing lesions mimicking glioblastoma or metastasis. In this article, we describe clinicoradiologic features and test the performance of DSC-PWI metrics for presurgical identification. Patients without AIDS with histologically confirmed diffuse large B-cell Epstein-Barr virus-positive primary CNS lymphoma (December 2010 to January 2022) and diagnostic MR imaging without onco-specific treatment were retrospectively studied. Clinical, demographic, and conventional imaging data were reviewed. Previously published DSC-PWI time-intensity curve analysis methodology, to presurgically identify primary CNS lymphoma, was used in this particular lymphoma subtype and compared with a prior cohort of 33 patients with Epstein-Barr virus-negative CNS lymphoma, 35 with glioblastoma, and 36 with metastasis data. Normalized curves were analyzed and compared on a point-by-point basis, and previously published classifiers were tested. The standard percentage of signal recovery and CBV values were also evaluated. Seven patients with Epstein-Barr virus-positive primary CNS lymphoma were included in the study. DSC-PWI normalized time-intensity curve analysis performed the best for presurgical identification of Epstein-Barr virus-positive CNS lymphoma (area under the receiver operating characteristic curve of 0.984 for glioblastoma and 0.898 for metastasis), followed by the percentage of signal recovery (0.833 and 0.873) and CBV (0.855 and 0.687). When a necrotic tumor is found in a potentially immunocompromised host, neuroradiologists should consider Epstein-Barr virus-positive CNS lymphoma. DSC-PWI could be very useful for presurgical characterization, with especially strong performance of normalized time-intensity curves.

Cluster Analysis of DSC MRI, Dynamic Contrast-Enhanced MRI, and DWI Parameters Associated with Prognosis in Patients with Glioblastoma after Removal of the Contrast-Enhancing Component: A Preliminary Study.

No report has been published on the use of DSC MR imaging, DCE MR imaging, and DWI parameters in combination to create a prognostic prediction model in glioblastoma patients. The aim of this study was to develop a machine learning-based model to find preoperative multiparametric MR imaging parameters associated with prognosis in patients with glioblastoma. Normalized CBV, volume transfer constant, and ADC of the nonenhancing T2 high-signal-intensity lesions were evaluated using K-means clustering. A total of 142 patients with glioblastoma who underwent preoperative MR imaging and total resection were included in this retrospective study. From the normalized CBV, volume transfer constant, and ADC maps, the parametric data were sorted using the K-means clustering method. Patients were divided into training and test sets (ratio, 1:1), and the optimal number of clusters was determined using receiver operating characteristic analysis. Kaplan-Meier survival analysis and log-rank tests were performed to identify potential parametric predictors. A multivariate Cox proportional hazard model was conducted to adjust for clinical predictors. The nonenhancing T2 high-signal-intensity lesions were divided into 6 clusters. The cluster (class 4) with the relatively low normalized CBV and volume transfer constant value and the lowest ADC values was most associated with predicting glioblastoma prognosis. The optimal cutoff of the class 4 volume fraction of nonenhancing T2 high-signal-intensity lesions predicting 1-year progression-free survival was 9.70%, below which the cutoff was associated with longer progression-free survival. Two Kaplan-Meier curves based on the cutoff value showed a statistically significant difference (P = .037). When we adjusted for all clinical predictors, the cluster with the relatively low normalized CBV and volume transfer constant values and the lowest ADC value was an independent prognostic marker (hazard ratio, 3.04; P = .048). The multivariate Cox proportional hazard model showed a concordance index of 0.699 for progression-free survival. Our model showed that nonenhancing T2 high-signal-intensity lesions with the relatively low normalized CBV, low volume transfer constant values, and the lowest ADC values could serve as useful prognostic imaging markers for predicting survival outcomes in patients with glioblastoma.

Xingnao Kaiqiao Acupuncture Combined with Butylphthalide Sodium Chloride Injection in the Treatment of Acute Cerebral Infarction and Its Effect on the Levels of Serum Malondialdehyde, Superoxide Dismutase, and Glutathione Peroxidase.

Objective The aim of this study is to explore the therapeutic effect of Xingnao kaiqiao acupuncture combined with butylphthalide sodium chloride injection on acute cerebral infarction and its effect on the levels of serum malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH). Methods 120 patients with acute cerebral infarction who were treated in our hospital from March 2020 to March 2022 and met the inclusion and exclusion criteria were divided into two groups. The control group was treated with sodium butylphthalide chloride injection, and the study group was treated with Xingnao kaiqiao acupuncture combined with sodium butylphthalide chloride injection. Results After treatment, the levels of neurotransmitters, the TTP and RI and MDA in both groups decreased, and the Qmean, CBV values, and the levels of SOD and GSH increased, and the changes of index in the study group were more significant than those in the control group (P < 0.05). After treatment, the NIHSS score and syndrome score of the two groups decreased, the MMSE score increased, the NIHSS score and syndrome score of the study group decreased more significantly than that of the control group, and MMSE score increased more significantly than that of the control group (P < 0.05). In terms of clinical efficacy, the total effective rate of the study group was higher than that of the control group (P < 0.05). Conclusion Xingnao kaiqiao acupuncture combined with butylphthalide sodium chloride injection is effective in patients with acute cerebral infarction. It can improve the level of neurotransmitters and cerebral blood flow perfusion and inhibit the abnormal expression of MDA, SOD, and GSH.

The Effect of Hemoglobin Concentration on Hyperbaric Oxygen and Non-hyperbaric Oxygen in the Treatment of Hypertensive Intracerebral Hemorrhage After Operation at the High Altitude.

BackgroundThe prognosis of hypertensive intracerebral hemorrhage (HICH) is poor at high altitudes. The objective of this study was to explore whether hyperbaric oxygen (HBO) can improve the results of computed tomography perfusion (CTP) imaging and the neurological function of patients with HICH, and influence the hemoglobin concentration.MethodThe patients with HICH were treated with puncture and drainage. Twenty-one patients (51.22% of 41 patients in total) were treated with HBO after the operation, and the other patients received conventional treatment. CTP was performed twice, and all indices were measured. Scatter plots were used to determine the effect of hemoglobin concentration on CTP imaging. Receiver operating characteristic (ROC) curves were plotted to analyze the effects of hemoglobin concentration and hematoma volume on recovery results. The patients were followed up for 6 months.ResultsForty-one patients with HICH were treated with puncture and drainage. In total, 21 were treated with HBO after the operation, and 20 received conventional treatment as the control group. No significant differences in the CBV and CBF values of the two groups were noted before treatment. After 10 days, the values of CBV and CBF in the HBO group were significantly higher than those in the control group. A scatter diagram showed there was no significant in the HBO group, but significant correlation for the CBV and CBF values in the control group’s hematoma center and margin. The ROC curves showed that hematoma volume had an influence on prognosis of the control group. The Glasgow Coma Scale (GOS) scores of the HBO group were significantly higher than those of the control group (p < 0.05).ConclusionsHBO therapy can improve the postoperative CBV and CBF values of patients with HICH and ameliorate their prognoses. There was no significant correlation between HBO group and hemoglobin concentration on admission.

Volumetric Measurement of Relative CBV Using T1-Perfusion-Weighted MRI with High Temporal Resolution Compared with Traditional T2*-Perfusion-Weighted MRI in Postoperative Patients with High-Grade Gliomas.

T1-PWI with high temporal resolution may provide a reliable relative CBV value as a valid alternative to T2*-PWI under increased susceptibility. The purpose of this study was to assess the technical and clinical performance of T1-relative CBV in patients with postoperative high-grade gliomas. Forty-five MRIs of 34 patients with proved high-grade gliomas were included. In all MRIs, T1- and T2*-PWIs were both acquired and processed semiautomatically to generate relative CBV maps using a released commercial software. Lesion masks were overlaid on the relative CBV maps, followed by a histogram of the whole VOI. The intraclass correlation coefficient and Bland-Altman plots were used for quantitative and qualitative comparisons. Signal loss from both methods was compared using the Wilcoxon signed-rank test of zero voxel percentage. The MRIs were divided into a progression group (n = 20) and a nonprogression group (n = 14) for receiver operating characteristic curve analysis. Fair intertechnique consistency was observed between the 90th percentiles of the T1- and T2*-relative CBV values (intraclass correlation coefficient = 0.558, P < .001). T2*-PWI revealed a significantly higher percentage of near-zero voxels than T1-PWI (17.7% versus 3.1%, P < .001). There was no statistically significant difference between the area under the curve of T1- and T2*-relative CBV (0.811 versus 0.793, P = .835). T1-relative CBV showed 100% sensitivity and 57.1% specificity for the detection of progressive lesions. T1-relative CBV demonstrated exquisite diagnostic performance for detecting progressive lesions in postoperative patients with high-grade gliomas, suggesting the potential role of T1-PWI as a valid alternative to the traditional T2*-PWI.

Added Value of Contrast Leakage Information over the CBV Value of DSC Perfusion MRI to Differentiate between Pseudoprogression and True Progression after Concurrent Chemoradiotherapy in Glioblastoma Patients

Added Value of Contrast Leakage Information over the CBV Value of DSC Perfusion MRI to Differentiate between Pseudoprogression and True Progression after Concurrent Chemoradiotherapy in Glioblastoma Patients

Hypovascular Cellular Tumor in Primary Central Nervous System Lymphoma is Associated with Treatment Resistance: Tumor Habitat Analysis Using Physiologic MRI.

The microenvironment of lymphomas is known to be highly variable and closely associated with treatment resistance and survival. We tried to develop a physiologic MR imaging-based spatial habitat analysis to identify regions associated with treatment resistance to facilitate the prediction of tumor response after initial chemotherapy in patients with primary central nervous system lymphoma. Eighty-one patients with pathologically confirmed primary central nervous system lymphoma were enrolled. Pretreatment physiologic MR imaging was performed, and K-means clustering was used to separate voxels into 3 spatial habitats according to ADC and CBV values. Associations of spatial habitats and clinical and conventional imaging predictors with time to progression were analyzed using Cox proportional hazards modeling. The performance of statistically significant predictors for time to progression was assessed using the concordance probability index. The 3 spatial habitats of hypervascular cellular tumor, hypovascular cellular tumor, and hypovascular hypocellular tumor were identified. A large hypovascular cellular habitat was most significantly associated with short time to progression (hazard ratio, 2.83; P = . 017). The presence of an atypical finding (hazard ratio, 4.41; P = . 016), high performance score (hazard ratio, 5.82; P = . 04), and high serum lactate dehydrogenase level (hazard ratio, 1.01; P = .013) was significantly associated with time to progression. A predictive model constructed using the habitat score and other imaging parameters showed a concordance probability index for prediction of time to progression of 0.70 (95% CI, 0.54-0.87). A hypovascular cellular tumor habitat is associated with treatment resistance in primary central nervous system lymphoma, and its assessment may refine prechemotherapy imaging-based response prediction for patients with primary central nervous system lymphoma.

Perfusion Imaging Collateral Scores Predict Infarct Growth in Non-Reperfused DEFUSE 3 Patients

ObjectiveThis study evaluated the associations of perfusion imaging collateral profiles with radiographic and clinical outcome in late presenting, non-reperfused patients in the DEFUSE 3 clinical trial. MethodsNon-reperfused patients in both treatment arms were included. Baseline ischemic core, Tmax >6s, and Tmax >10s perfusion volumes were calculated with RAPID software; infarct volumes obtained 24 hours after randomization were manually determined from DWI or CT. Substantial infarct growth was defined as a >25mL increase between baseline and 24-hour follow-up. Hypoperfusion Intensity Ratio (HIR) was defined as the proportion of the Tmax >6s lesion with Tmax >10s delay; CBV index was calculated by RAPID from mean CBV values within the Tmax >6s lesion compared to regions of normal CBV. ResultsEighty-four patients were included. ROC analysis showed HIR ≥0.34 (AUC=0.68) and CBV index ≤0.74 (AUC=0.72) optimally predicted substantial infarct growth in follow-up. Median growth was 23.4 versus 73.2mL with HIR threshold of 0.34 (p=0.005), and 24.3 versus 58.7mL with CBV index threshold of 0.74 (p=0.004). If baseline HIR and CBV index were both favorable, median growth was 21.7mL, 40.9mL if one was favorable, and 108.2mL if both were unfavorable (p<0.001). Baseline perfusion profile was not associated with 90-day functional outcome. ConclusionsPerfusion collateral scores forecast infarct growth in late presenting, non-reperfused ischemic stroke patients. These parameters may be useful for guiding transfer decisions, such as need for repeat imaging upon thrombectomy center arrival, and may help identify slow progressing patients more likely to have persistent salvageable ischemic tissue beyond 24 hours.

Contrast Bolus Interference in a Multimodal CT Stroke Protocol.

Whether CTP is performed before or after CTA varies within multimodal CT stroke protocols. CTA after CTP might show venous filling, and CTP metrics might be disturbed by prior CTA. Therefore, we compared CTP metrics conducted before and after CTA in a large cohort of patients with stroke and analyzed interferences of the CTA bolus with the CTP measurement. We analyzed 1980 patients (368 patients with CTP performed before CTA [group A] versus 1612 patients with CTP performed after [group B]) in a retrospective study. Mean curves, histograms of CTP baseline Hounsfield units, CBF, CBV, time-to-maximum, hypoperfusion, and core volumes were calculated using the software VEOcore. CTA and CTP interferences were analyzed, and a detection and correction method was proposed. Mean CTP baseline values were significantly different in both groups (41 versus 45 HU within the groups A and B, respectively). However, perfusion metrics, hypoperfusion, and core volumes yielded no significant differences. In 49 patients, the descending flank of the CTA bolus interfered with the baseline of the CTP measurement, leading to erroneously low CBV values. These errors vanished when a correction method was applied. CTP can be reliably performed after CTA without a relevant net effect on perfusion metrics. However, when measuring CTP after CTA, either a short pause on the order of 30 seconds should be observed or an appropriate correction method should be applied. It may help to avoid excluding patients from mechanical thrombectomy by overestimating infarct cores.

Comparison of Blood Perfusion Parameters in the Ipsilateral and Contralateral Sides of the Brain in Known Cases of Mesial Temporal Lobe Epilepsy

Background: Temporal lobe epilepsy (TLE) is the most common form of focal seizures. To localize the epileptic site for surgery, different neuroimaging tools are used. Perfusion magnetic resonance imaging (MRI) is one of the modalities used to evaluate the cerebral hemodynamics and localize intracranial neoplasia and cerebrovascular events. Two contrast-based perfusion imaging sequences are described, including dynamic susceptibility contrast-enhanced MRI (DSC-MRI) and dynamic contrast-enhanced MRI (DCE-MRI). The most commonly measured parameters include the relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and mean transit time (MTT). Objectives: This study aimed to evaluate the blood perfusion parameters, such as rCBV and rCBF, in patients diagnosed with mesial temporal lobe epilepsy (MTLE), using DSC-perfusion MRI to determine whether there is a change in these parameters and if this modality can be used to diagnose and localize the epileptic side. Patients and Methods: Twenty-two patients, who were diagnosed with TLE clinically and electrophysiologically by a neurologist, were investigated in this study. The patients were examined for the presence of any other lesions, such as tumors or cerebrovascular disease as the exclusion criteria. Perfusion images were processed by the Siemens perfusion software, and the rCBV and rCBF maps were generated based on the gamma variate fit. For qualitative analysis, coronal reconstruction of rCBV and rCBF maps was performed. For quantitative analysis, a single neuroradiologist placed the region of interest (ROI) on the hippocampus and the parahippocampal gyrus on T1W images at the same level of DSC images. After determining the CBV and CBF values relative to the ROI of each side, the asymmetry index (AI) was calculated. Results: In patients with unilateral epilepsy, the blood perfusion parameters in the ipsilateral side of the brain were significantly lower than the contralateral side (P &lt; 0.0001); the mean values of both parameters were significantly lower in the affected side as compared to the opposite side. Conclusion: In patients with TLE, significantly lower blood perfusion parameters in the affected side of the brain can help radiologists and neurologists to lateralize the MTLE side.

MGMT Promoter Methylation Status in Initial and Recurrent Glioblastoma: Correlation Study with DWI and DSC PWI Features.

O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status in primary and recurrent glioblastoma may change during treatment. The purpose of this study was to correlate MGMT promoter methylation status changes with DWI and DSC PWI features in patients with recurrent glioblastoma after standard treatment. Between January 2008 and November 2016, forty patients with histologically confirmed recurrent glioblastoma were enrolled. Patients were divided into 3 groups according to the MGMT promoter methylation status for the initial and recurrent tumors: 2 groups whose MGMT promoter methylation status remained, group methylated (n = 13) or group unmethylated (n = 18), and 1 group whose MGMT promoter methylation status changed from methylated to unmethylated (n = 9). Normalized ADC and normalized relative CBV values were obtained from both the enhancing and nonenhancing regions, from which histogram parameters were calculated. The ANOVA and the Kruskal-Wallis test followed by post hoc tests were performed to compare histogram parameters among the 3 groups. The t test and Mann-Whitney U test were used to compare parameters between group methylated and group methylated to unmethylated. Receiver operating characteristic curve analysis was used to measure the predictive performance of the normalized relative CBV values between the 2 groups. Group methylated to unmethylated showed significantly higher means and 90th and 95th percentiles of the cumulative normalized relative CBV values of the nonenhancing region of the initial tumor than group methylated and group unmethylated (all P < .05). The mean normalized relative CBV value of the nonenhancing region of the initial tumor was the best predictor of methylation status change (P < .001), with a sensitivity of 77.78% and specificity of 92.31% at a cutoff value of 2.594. MGMT promoter methylation status might change in recurrent glioblastoma after standard treatment. The normalized relative CBV values of the nonenhancing region at the first preoperative MR imaging were higher in the MGMT promoter methylation change group from methylation to unmethylation in recurrent glioblastoma.

Spatiotemporal habitats from multiparametric physiologic MRI distinguish tumor progression from treatment-related change in post-treatment glioblastoma.

We aimed to develop multiparametric physiologic MRI-based spatial habitats and to evaluate whether temporal changes in these habitats help to distinguish tumor progression from treatment-related change in post-treatment glioblastoma. This retrospective, single-institution study included patients with glioblastoma treated by concurrent chemoradiotherapy who had newly developed or enlarging, measurable contrast-enhancing mass. Contrast-enhancing mass was divided into three spatial habitats by K-means clustering of voxel-wise ADC and CBV values. Temporal changes of these habitats between two consecutive examinations prior to the diagnosis of tumor progression or treatment-related change were assessed. Predictors were selected using logistic regression and the performance was measured with an area under the receiver operating characteristics curve (AUC). Spatiotemporal habitats were further analyzed for correlation with the site of tumor progression. There were 75 patients (mean, 58 years; range, 26-81 years; 43 men) with 48 cases of tumor progression and 39 cases of treatment-related change including 12 patient overlaps at different time points. Three spatial habitats of hypervascular cellular, hypovascular cellular, and nonviable tissue were identified. Increase in the hypervascular cellular (OR 4.55, p = .002) and hypovascular cellular habitat (OR 1.22, p < .001) was predictive of tumor progression. Combination of spatiotemporal habitats yielded a high diagnostic performance with an AUC of 0.89 (95% CI, 0.87-0.92). An increase in hypovascular cellular habitat predicted the site of tumor progression in 84% [21/25] of cases with tumor progression. Temporal changes in spatial habitats derived from multiparametric physiologic MRI provided diagnostic value in distinguishing tumor progression from treatment-related change and predicted site of tumor progression in post-treatment glioblastoma. • In post-treatment glioblastoma, three spatial habitats of hypervascular cellular, hypovascular cellular, and nonviable tissue were identified, and an increase in the hypervascular cellular (OR 4.55, p = .002) and hypovascular cellular habitat (OR 1.22, p < .001) was predictive of tumor progression. • Combination of spatiotemporal habitats yielded a high diagnostic performance with an AUC of 0.89 (95% CI, 0.87-0.92). • An increase in hypovascular cellular habitat predicted the site of tumor progression in 84% (21/25) of cases with tumor progression.

Imaging glioma biology: spatial comparison of amino acid PET, amide proton transfer, and perfusion-weighted MRI in newly diagnosed gliomas

PurposeImaging glioma biology holds great promise to unravel the complex nature of these tumors. Besides well-established imaging techniques such O-(2-[18F]fluoroethyl)-l-tyrosine (FET)-PET and dynamic susceptibility contrast (DSC) perfusion imaging, amide proton transfer–weighted (APTw) imaging has emerged as a promising novel MR technique. In this study, we aimed to better understand the relation between these imaging biomarkers and how well they capture cellularity and vascularity in newly diagnosed gliomas.MethodsPreoperative MRI and FET-PET data of 46 patients (31 glioblastoma and 15 lower-grade glioma) were segmented into contrast-enhancing and FLAIR-hyperintense areas. Using established cutoffs, we calculated hot-spot volumes (HSV) and their spatial overlap. We further investigated APTw and CBV values in FET-HSV. In a subset of 10 glioblastoma patients, we compared cellularity and vascularization in 34 stereotactically targeted biopsies with imaging.ResultsIn glioblastomas, the largest HSV was found for APTw, followed by PET and CBV (p < 0.05). In lower-grade gliomas, APTw–HSV was clearly lower than in glioblastomas. The spatial overlap of HSV was highest between APTw and FET in both tumor entities and regions. APTw correlated significantly with cellularity, similar to FET, while the association with vascularity was more pronounced in CBV and FET.ConclusionsWe found a relevant spatial overlap in glioblastomas between hotspots of APTw and FET both in contrast-enhancing and FLAIR-hyperintense tumor. As suggested by earlier studies, APTw was lower in lower-grade gliomas compared with glioblastomas. APTw meaningfully contributes to biological imaging of gliomas.

TRLS-02. A PILOT STUDY OF EVALUATING EARLY TREATMENT RESPONSE OF BRAIN METASTASES AFTER STEREOTACTIC RADIOSURGERY USING DYNAMIC SUSCEPTIBILITY-WEIGHTED PERFUSION MAGNETIC RESONANCE IMAGING

PURPOSE: To determine if dynamic susceptibility-weighted perfusion magnetic resonance imaging (DSC-PMR) can be used to predict local recurrence (LR) of brain metastases after stereotactic radiosurgery (SRS). METHODS: This is a prospective observational study of adult brain metastasis patients treated with single-fraction SRS, who were imaged with DSC-PMRs before SRS and after 1 week. DSC-PMRs were performed with tracer method in which injection of gadolinium was followed by repeated T2*-weighted gradient echo-planar image acquisition. Regions of interests (ROIs) were generated based on the T1-enhancing tumors irradiated. Relative cerebral blood volume (rCBV) and relative cerebral blood flow (rCBF) parameter maps were calculated by dividing the top 5% of CBV or CBF values within a ROI by the contralateral normal thalamus. LR was determined according to the RECIST 1.1 criteria. Cox regression was conducted to identify factors associated with time to LR. LR rates were estimated with the Kaplan-Meier method and compared using log-rank test. RESULTS: Twenty-three patients were enrolled from 2013 through 2016, with 24 evaluable lesions from 17 patients. After a median follow-up of 12.8 months (range: 3.0–53.7), 5 lesions (21%) developed LR after a median of 3.4 months (range: 2.3–5.7). On univariable analysis, higher rCBV at week 1 (HR 1.06, 95% CI 1.01–1.11, p=0.02), lower SRS dose (HR 0.43, 95% CI 0.20–0.91, p=0.03), and larger tumor volume (HR 1.52, 95% CI 1.05–2.20, p=0.03) were significantly associated with LR, but not histology, rCBV at baseline, change of rCBV at week 1 from baseline, or any rCBF parameters. Higher rCBV at week 1 (above the median) was associated with significantly higher risk of LR than lower rCBV (44% vs 0% at 1 year, respectively, p=0.02). CONCLUSIONS: DSC-PMR and specifically rCBV at week 1 may be a promising imaging biomarker to predict treatment response of brain metastasis after SRS and warrant further investigation.

IDH genotypes differentiation in glioblastomas using DWI and DSC-PWI in the enhancing and peri-enhancing region.

Isocitrate dehydrogenase (IDH) mutation has diagnostic and prognostic values in glioblastomas. Peritumoral invasion of glioma cells is a cardinal feature of glioblastomas. To evaluate the contribution of DWI and DSC-PWI in the enhancing and peri-enhancing region for discriminating glioblastomas IDH genotypes, and the diagnostic values of combining two techniques in the peri-enhancing region compared with those in the enhancing region. We retrospectively reviewed the conventional MRI (cMRI), DWI and DSC-PWI obtained from 10 patients with IDH-mutated (IDH-m) glioblastomas and 65 patients with IDH wild-type (IDH-w) glioblastomas. Features of cMRI, relative minimum ADC in the enhancing region (rADCmin-t) and peri-enhancing area (rADCmin-p), and relative maximum CBV values in the enhancing region (rCBVmax-t) and peri-enhancing region (rCBVmax-p) were compared between two groups. Receiver operating characteristic curves and logistic regression analysis were used to assess diagnostic performance. IDH-m glioblastomas tended to present in frontal lobes and younger patients. The rADCmin-t (P=0.042) were significantly lower in IDH-w than IDH-m. Both rCBVmax-t and rCBVmax-p showed significant differences between two subgroups (all P<0.001). The optimal cutoff values in prediction of IDH-m were >0.98 for rADCmin-t, <7.27 for rCBVmax-t, and < 0.97 for rCBVmax-p. Multivariate logistic regression revealed that the combination of rADCmin-t and rCBVmax-t yielded the highest sensitivity and specificity. The rCBVmax-t or rCBVmax-p may serve as preferable and comparable imaging biomarkers for evaluation of glioblastomas IDH status. The combination of rADCmin-t and rCBVmax-t may yield the maximum predictive power for differentiating IDH status.