Low rCBV Research Articles

Integrating Diffusion-weighted and Perfusion-weighted Imaging for Improved Grading and Characterization of Brain Tumors

Objective: This study aims to evaluate the role of Diffusion-Weighted Imaging (DWI) and Perfusion-Weighted Imaging (PWI) in the detection, characterization, and grading of brain tumors, focusing on their correlation with histopathological findings. Materials and Methods: A total of 40 patients with intracranial mass lesions underwent DWI, PWI, and conventional MRI using a 1.5 Tesla MRI scanner. Apparent Diffusion Coefficient (ADC) values were calculated for tumor core, peritumoral edema, and normal brain tissue. Cerebral Blood Volume (CBV), Cerebral Blood Flow (CBF), and Mean Transit Time (MTT) were analyzed using PWI. Data were statistically analyzed, with a p-value ≤ 0.05 considered significant. Results: The study included 38 neoplastic lesions and 2 tuberculomas. DWI showed distinct ADC values for different tumors, with meningiomas having a mean ADC of 0.84 ± 0.3 × 10⁻³ mm²/s and schwannomas a higher ADC of 2.14 × 10⁻³ mm²/s. PWI revealed elevated relative CBV in high-grade gliomas (mean: 2.1 ± 0.76), while lower rCBV was observed in metastases (mean: 0.5 ± 0.26). Tuberculomas exhibited intermediate perfusion characteristics. Conclusion: DWI and PWI, in conjunction with conventional MRI, enhance the diagnostic accuracy for brain tumors by providing valuable information on tumor cellularity and vascularity. These techniques aid in distinguishing between tumor types, grades, and associated edema, thus improving clinical decision-making and treatment planning.

Low rCBV values in glioblastoma tumor progression under chemoradiotherapy.

After standard treatment for glioblastoma, perfusion MRI remains challenging for differentiating tumor progression from post-treatment changes. Our objectives were (1) to correlate rCBV values at diagnosis and at first tumor progression and (2) to analyze the relationship of rCBV values at tumor recurrence with enhancing volume, localization of tumor progression, and time elapsed since the end of radiotherapy in tumor recurrence. Inclusion criteria were (1) age > 18years, (2) histologically confirmed glioblastoma treated with STUPP regimen, and (3) tumor progression according to RANO criteria > 12weeks after radiotherapy. Co-registration of segmented enhancing tumor VOIs with dynamic susceptibility contrast perfusion MRI was performed using Olea Sphere software. For tumor recurrence, we correlated rCBV values with enhancing tumor volume, with recurrence localization, and with time elapsed from the end of radiotherapy to progression. Analyses were performed with SPSS software. Sixty-four patients with glioblastoma were included in the study. Changes in rCBV values between diagnosis and first tumor progression were significant (p < 0.001), with a mean and median decreases of 32% and 46%, respectively. Mean rCBV values were also different (p < 0.01) when tumors progressed distally (radiation field rCBV values of 1.679 versus 3.409 distally). However, changes and, therefore, low rCBV values after radiotherapy in tumor recurrence were independent of time. Chemoradiation alters tumor perfusion and rCBV values may be decreased in the setting of tumor progression. Changes in rCBV values with respect to diagnosis, with low rCBV in tumor progression, are independent of time but related to the site of recurrence.

IMAGING HABITAT CHANGES AFTER PREOPERATIVE RADIOTHERAPY FOR GLIOBLASTOMA: UTILISATION OF A BIOINFORMATICS AND MACHINE LEARNING PIPELINE TO CHARACTERISE REGIONAL TREATMENT RESPONSE

Abstract AIMS Imaging of tumour habitats is a novel technique to assess regional treatment response by defining tumour ‘habitats’, which are regions with shared imaging characteristics. Here, we describe a novel pipeline to characterise imaging habitats in glioblastoma using bioinformatics and machine learning. We apply this pipeline to glioblastoma patients in the Preoperative Brain Irradiation in Glioblastoma (POBIG) trial that received preoperative radiotherapy for the first time. METHOD Glioblastoma patients underwent preoperative diffusion/perfusion MRI. A two- stage clustering pipeline was developed to define imaging habitats using relative cerebral blood volume (rCBV) and apparent diffusion co- effcient (ADC). 6 habitats were defined that occupied 10.6-21.5% of tumour volume. Treatment response was evaluated using Ktrans permeability. RESULTS In newly diagnosed cases the commonest habitats included those with a medium and high rCBV. In contrast, recurrent cases had significantly greater proportion of low rCBV habitats (p = 0.026). Two patients in the POBIG trial received 8 Gy preoperative radiotherapy. Within 24 hours of treatment there was a global decrease in vascularity with a decrease in high rCBV habitats (-3.7%) and increase in low rCBV habitats (+8.2%) in irradiated regions. Habitats demonstrated a heterogeneous response to preoperative radiotherapy, with a greater increase in Ktrans in high rCBV habitats (mean +83%) versus low rCBV habitats (mean +40%). CONCLUSIONS We have developed a unique pipeline to delineate imaging habitats in glioblastoma and applied it to a novel trial. Imaging habitats can allow regional monitoring of treatment response and could allow more targeted treatment in future.

Correlation between Perfusion-Weighted Magnetic Resonance Imaging (MRI) Features with Histopathological Grading of Glioma

Background: Gliomas are the most common primary neoplasm of the brain. It histopathologically grades I to IV. I and II are low grade while III, IV are high grade. Low-grade gliomas are usually subject to either strict follow-up or surgery. The treatment for high grade gliomas is typically surgery, followed by concomitant radiation therapy and chemotherapy. Conventional MRI has limitations for the grading of gliomas. In addition to conventional MRI techniques, a variety of new techniques such as perfusion-weighted MRI which noninvasively measures cerebral perfusion that can be used for better assessment of glioma. This will be helpful for therapeutic approach and counseling about prognosis of the patient. Methods: This cross sectional observational study was conducted in the Department of Neurosurgery, Bangabandhu Sheikh Mujib Medical University from IRB clearance to 18 months. The patients who fulfill the selection criteria were enrolled in this study. Written informed consent was taken from the patients and/or the legal guardian/ responsible family members after completely explaining to them the procedure and the purpose of the study. Patient’s data was collected in questionnaire/data collection sheet. The privacy of the patient was strictly maintained and the patient’s information will not be disclosed to any source. The study data will only be used for the purpose of this scientific study. This study was not causing any additional harm to the patients. All the patients were evaluated by a standard conventional contrast-enhanced study with perfusion-weighted image on Siemens 3 Tesla MRI. The histopathological grading of the tumor was done as per the WHO classification of 2007. Then correlation was done between PWI finding and WHO histopathological grading. Results: Measurement of relative cerebral blood volume in glioma patients was done in PW-MRI preoperatively. Out of the 35 tumors evaluated, 17 were found as low rCBV and 18 as high. Histopathological examination of glioma was done postoperatively. Among 35 tumors, 19 are low grade gliomas and 16 are high grade gliomas. For the correlation between relative cerebral blood volume in preoperative PW MRI and histopathological grading of glioma, Spearman’s Rank Correlation Coefficient Test was done. We found a significant positive coefficient value of r = 0.572 with a significant p-value of p = &lt;0.001. A single cutoff relative cerebral blood volume value of 1.7 for low versus high grade glioma was found to be 77.8% sensitive and 88.2% specific. Conclusion: The present study ascertains that histopathological grading of glioma is positively correlated with relative cerebral blood volume in PW MRI. Bang. J Neurosurgery 2022; 12(1): 12-19

MR Perfusion Imaging as a Problem- Solving Tool for Differentiating High-grade Glioma and Tumefactive Demyelination: A Report of Two Cases

Clinically, it is nearly impossible to differentiate between high-grade glioma, specifically Glioblastoma Multiforme (GBM), and Tumefactive Demyelination (TMD). Radiologically, distinguishing between GBM and TMD is challenging since they show similar findings on Computed Tomography (CT) and Magnetic Resonance Imaging (MRI). To avoid invasive procedures that may increase patient morbidity, the use of MR perfusion imaging is highlighted in these case reports. We present two cases of young adult females with neurological deficits. The first case involves an 18-year-old female who presented with a dull, intermittent, holocephalic headache for eight months, along with heaviness and recent onset of pain in the right upper limb. MR spectroscopy revealed an increased choline/creatinine ratio at the margins of the lesion, measuring approximately 2.4, with a decrease in N-Acetylaspartate (NAA) and NAA/Creatinine. Based on these findings, the possibility of either high-grade glioma or TMD was considered. Further evaluation using perfusion imaging showed a substantial increase in the mean relative Cerebral Blood Volume (rCBV) within the lesion, suggesting a higher likelihood of high-grade glioma rather than TMD. Biopsy confirmed the diagnosis as high-grade glioma (GBM), revealing marked mitotic changes with nuclear pleomorphism and multinucleated cells. The second case involves a 22-year- old female who presented with left upper limb and lower limb weakness for 10 days. MR spectroscopy showed reduced NAA values and an elevated choline peak with small lactate at a few places. A choline/creatine ratio of 1.9 was obtained. On perfusion imaging, the observed mean rCBV values were substantially low (rCBV measuring approximately 1.07). Consequently, a final radiological diagnosis of TMD was considered. A biopsy confirmed the presence of inflammatory demyelination.

Association of concomitant headache with hypoperfusion in ischemic stroke: A multimodal CT-based study.

Previous investigations indicate that vessel wall elasticity may contribute to the occurrence of an ischemic stroke-associated headache. In this prospective study, the association between radiologic parameters of intracranial hemodynamic changes and concomitant headaches during the early phase of ischemic stroke was examined. Consecutive patients with acute ischemic stroke (AIS) from the First Affiliated Hospital of Soochow University were recruited and divided into two groups according to their questionnaire results and the International Classification of Headache Disorder 3 criteria. Baseline data, including stroke sub-types and neurological function, at admission and discharge were collected. Non-contrast computed tomography (CT), CT angiography, and CT perfusion were performed to assess intracranial hemodynamic changes. Multiple adjusted logistic models were used and possible confounding factors were included in sequential models. A total of 190 patients with AIS (93 headaches and 97 non-headache) were recruited. There were significant differences between the two groups in gender, hypertension, Alberta stroke program early CT score, relative cerebral blood flow (rCBF), and relative cerebral blood volume (rCBV). Furthermore, rCBV (adjusted odds ratio [OR] 0.160; 95% confidence interval [CI], 0.055-0.461; p < 0.001) and rCBF (adjusted OR, 0.309; 95% CI, 0.113-0.844; p < 0.05) were significantly associated with concomitant headache during the early phase of AIS in fully adjusted models. After adjusting for sociodemographic characteristics and other confounding factors, p values for the ORs were robust and intensified. Patients with lower rCBV and rCBF tended to experience the concomitant headache during the early phase of AIS. Regional hypoperfusion and microcirculation might play an important role in this separate clinical entity.

Impact of relative cerebral blood volume reduction on early neurological improvement in extensive ischemic stroke.

The benefit of endovascular treatment (EVT) for patients with low Alberta Stroke Program early computed tomography score (ASPECTS) is still ambiguous and is currently being investigated in randomized trials. Computed tomography (CT) perfusion, used to estimate infarct extent and progression, might predict early neurological improvement (ENI) after EVT. We hypothesized that the degree of relative cerebral blood volume (rCBV) reduction is directly associated with ENI in low ASPECTS patients undergoing EVT. Ischemic stroke patients with ASPECTS ≤ 5 who received multimodal CT and underwent thrombectomy were analyzed. rCBV reduction was defined as the ratio of cerebral blood volume (CBV), measured in the ischemic lesion to contralateral CBV. Complete reperfusion was defined as an expanded Thrombolysis in Cerebral Infarction score 2c-3. The clinical endpoint was ENI at 24 h, defined continuously (National Institutes of Health Stroke Scale [NIHSS] score change from baseline to 24 h) and binarized (NIHSS score at 24 h ≤ 8). A total of 102 patients were included. Lower rCBV reduction and complete EVT were independently associated with ENI (-11.4 NIHSS points, p= 0.04; -7.3 points, p&lt; 0.0001, respectively). The effect of complete EVT on ENI was directly linked to the degree of rCBV reduction: the probability for binary ENI was +34.6% (p= 0.004) in patients with low rCBV reduction versus +8.2% (p= 0.28) in patients with high rCBV reduction). In patients with ischemic stroke with low ASPECTS, ENI was directly linked to the degree of rCBV reduction, a potential indicator of ischemia depth in extensive baseline infarction. Lower rCBV reduction was associated with higher probability of ENI after complete reperfusion, suggesting less pronounced lesion progression despite its large extent and hence, a higher susceptibility to EVT.

Glioblastoma Stem-like Cell Detection Using Perfusion and Diffusion MRI.

Simple SummaryGlioblastoma stem-like cells (GSCs) are known to be aggressive and radio-resistant and proliferate heterogeneously in preferred environments. Additionally, quantitative diffusion and perfusion MRI biomarkers provide insight into the tissue micro-environment. This study assessed the sensitivity of these imaging biomarkers to GSCs in the hyperintensities-FLAIR region, where relapses may occur. A total of 16 patients underwent an MRI session and biopsies were extracted to study the GSCs. In vivo and in vitro biomarkers were compared and both Apparent Diffusion Coefficient (ADC) and relative Cerebral Blood Volume (rCBV) MRI metrics were found to be good predictors of GSCs presence and aggressiveness.Purpose: With current gold standard treatment, which associates maximum safe surgery and chemo-radiation, the large majority of glioblastoma patients relapse within a year in the peritumoral non contrast-enhanced region (NCE). A subpopulation of glioblastoma stem-like cells (GSC) are known to be particularly radio-resistant and aggressive, and are thus suspected to be the cause of these relapses. Previous studies have shown that their distribution is heterogeneous in the NCE compartment, but no study exists on the sensitivity of medical imaging for localizing these cells. In this work, we propose to study the magnetic resonance (MR) signature of these infiltrative cells. Methods: In the context of a clinical trial on 16 glioblastoma patients, relative Cerebral Blood Volume (rCBV) and Apparent Diffusion Coefficient (ADC) were measured in a preoperative diffusion and perfusion MRI examination. During surgery, two biopsies were extracted using image-guidance in the hyperintensities-FLAIR region. GSC subpopulation was quantified within the biopsies and then cultivated in selective conditions to determine their density and aggressiveness. Results: Low ADC was found to be a good predictor of the time to GSC neurospheres formation in vitro. In addition, GSCs were found in higher concentrations in areas with high rCBV. Conclusions: This study confirms that GSCs have a critical role for glioblastoma aggressiveness and supports the idea that peritumoral sites with low ADC or high rCBV should be preferably removed when possible during surgery and targeted by radiotherapy.

Demyelinating sentinel lesion preceding a primary central nervous system lymphoma.

A 29-year-old man presented with tonic-clonic seizures. Initial MRI showed a lesion centered on the white matter of the left frontal lobe, with restricted diffusion and contrast enhancement on its margins and low rCBV and hypometabolismon PET-CT, suggestive of a tumefactive demyelination lesion (). Patient underwent surgical biopsy, with no signs of malignancy (). Two months later, control MRI showed a new lesion on the brainstem, with solid enhancement and hypermetabolism on PET-CT, compatible with lymphoma ( and ). Demyelinating [...]

Noninvasive differentiation of molecular subtypes of adult nonenhancing glioma using MRI perfusion and diffusion parameters.

BackgroundNonenhancing glioma typically have a favorable outcome, but approximately 19–44% have a highly aggressive course due to a glioblastoma genetic profile. The aim of this retrospective study is to use physiological MRI parameters of both perfusion and diffusion to distinguish the molecular profiles of glioma without enhancement at presentation.MethodsNinety-nine patients with nonenhancing glioma were included, in whom molecular status (including 1p/19q codeletion status and IDH mutation) and preoperative MRI (T2w/FLAIR, dynamic susceptibility-weighted, and diffusion-weighted imaging) were available. Tumors were segmented semiautomatically using ITK-SNAP to derive whole tumor histograms of relative Cerebral Blood Volume (rCBV) and Apparent Diffusion Coefficient (ADC). Tumors were divided into three clinically relevant molecular profiles: IDH mutation (IDHmt) with (n = 40) or without (n = 41) 1p/19q codeletion, and (n = 18) IDH-wildtype (IDHwt). ANOVA, Kruskal-Wallis, and Chi-Square analyses were performed using SPSS.ResultsrCBV (mean, median, 75th and 85th percentile) and ADC (mean, median, 15th and 25th percentile) showed significant differences across molecular profiles (P < .01). Posthoc analyses revealed that IDHwt and IDHmt 1p/19q codeleted tumors showed significantly higher rCBV compared to IDHmt 1p/19q intact tumors: mean rCBV (mean, SD) 1.46 (0.59) and 1.35 (0.39) versus 1.08 (0.31), P < .05. Also, IDHwt tumors showed significantly lower ADC compared to IDHmt 1p/19q codeleted and IDHmt 1p/19q intact tumors: mean ADC (mean, SD) 1.13 (0.23) versus 1.27 (0.15) and 1.45 (0.20), P < .001).ConclusionsA combination of low ADC and high rCBV, reflecting high cellularity and high perfusion respectively, separates IDHwt from in particular IDHmt 1p/19q intact glioma.

Differentiation between glioblastoma and primary CNS lymphoma: application of DCE-MRI parameters based on arterial input function obtained from DSC-MRI.

This study aimed to evaluate whether arterial input functions (AIFs) obtained from dynamic susceptibility contrast (DSC)-MRI (AIFDSC) improve the reliability and diagnostic accuracy of dynamic contrast-enhanced (DCE)-derived pharmacokinetic (PK) parameters for differentiating glioblastoma from primary CNS lymphoma (PCNSL) compared with AIFs derived from DCE-MRI (AIFDCE). This retrospective study included 172 patients with glioblastoma (n = 147) and PCNSL (n = 25). All patients had undergone preoperative DSC- and DCE-MRI. The volume transfer constant (Ktrans), volume of the vascular plasma space (vp), and volume of the extravascular extracellular space (ve) were acquired using AIFDSC and AIFDCE. The relative cerebral blood volume (rCBV) was obtained from DSC-MRI. Intraclass correlation coefficients (ICC) and ROC curves were used to assess the reliability and diagnostic accuracy of individual parameters. The mean Ktrans, vp, and ve values revealed better ICCs with AIFDSC than with AIFDCE (Ktrans, 0.911 vs 0.355; vp, 0.766 vs 0.503; ve, 0.758 vs 0.657, respectively). For differentiating all glioblastomas from PCNSL, the mean rCBV (AUC = 0.856) was more accurate than the AIFDSC-driven mean Ktrans, which had the largest AUC (0.711) among the DCE-derived parameters (p = 0.02). However, for glioblastomas with low rCBV (≤ 75th percentile of PCNSL; n = 30), the AIFDSC-driven mean Ktrans and vp were more accurate than rCBV (AUC: Ktrans, 0.807 vs rCBV, 0.515, p = 0.004; vp, 0.715 vs rCBV, p = 0.045). DCE-derived PK parameters using the AIFDSC showed improved reliability and diagnostic accuracy for differentiating glioblastoma with low rCBV from PCNSL. • An accurate differential diagnosis of glioblastoma and PCNSL is crucial because of different therapeutic strategies. • In contrast to the rCBV from DSC-MRI, another perfusion imaging technique, the DCE parameters for the differential diagnosis have been limited because of the low reliability of AIFs from DCE-MRI. • When we analyzed DCE-MRI data using AIFs from DSC-MRI (AIFDSC), AIFDSC-driven DCE parameters showed improved reliability and better diagnostic accuracy than rCBV for differentiating glioblastoma with low rCBV from PCNSL.

Vascular habitat analysis based on dynamic susceptibility contrast perfusion MRI predicts IDH mutation status and prognosis in high-grade gliomas.

The current study aimed to evaluate the clinical practice for hemodynamic tissue signature (HTS) method in IDH genotype prediction in three groups derived from high-grade gliomas. Preoperative MRI examinations of 44 patients with known grade and IDH genotype were assigned into three study groups: glioblastoma multiforme, grade III, and high-grade gliomas. Perfusion parameters were analyzed and were used to automatically draw the four reproducible habitats (high-angiogenic enhancing tumor habitats, low-angiogenic enhancing tumor habitats, infiltrated peripheral edema habitats, vasogenic peripheral edema habitats) related to vascular heterogeneity. These four habitats were then compared between inter-patient with IDH mutation and their wild-type counterparts at these three groups, respectively. The discriminating potential for HTS in assessing IDH mutation status prediction was assessed by ROC curves. Compared with IDH wild type, IDH mutation had significantly decreased relative cerebral blood volume (rCBV) at the high-angiogenic enhancing tumor habitats and low-angiogenic enhancing tumor habitats. ROC analysis revealed that the rCBVs in habitats had great ability to discriminate IDH mutation from their wild type in all groups. In addition, the Kaplan-Meier survival analysis yielded significant differences for the survival times observed from the populations dichotomized by low (< 4.31) and high (> 4.31) rCBV in the low-angiogenic enhancing tumor habitat. The HTS method has been proven to have high prediction capabilities for IDH mutation status in high-grade glioma patients, providing a set of quantifiable habitats associated with tumor vascular heterogeneity. • The HTS method has a high accuracy for molecular stratification prediction for all subsets of HGG. • The HTS method can give IDH mutation-related hemodynamic information of tumor-infiltrated and vasogenic edema. • IDH-relevant rCBV difference in habitats will be a great prognosis factor in HGG.

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.

Combined analysis of MGMT methylation and dynamic-susceptibility-contrast MRI for the distinction between early and pseudo-progression in glioblastoma patients

IntroductionCurrently, no single diagnostic modality allows the distinction between early progression (EP) and pseudo-progression (Psp) in glioblastoma patients. Herein we aimed to identify the characteristics associated with EP and Psp, and to analyze their diagnostic value alone and in combination. Material and methodsWe reviewed the clinical, conventional magnetic resonance imaging (MRI), and molecular characteristics (MGMT promoter methylation, IDH mutation, and EGFR amplification) of glioblastoma patients who presented an EP (n=59) or a Psp (n=24) within six months after temozolomide radiochemotherapy. We analyzed relative cerebral blood volume (rCBV) and relative vessel permeability on K2 maps (rK2) in a subset of 33 patients using dynamic-susceptibility-contrast MRI. ResultsIn univariate analysis, EP was associated with neurological deterioration, higher doses of dexamethasone, appearance of a new enhanced lesion, subependymal enhancement, higher rCBV and rK2 values. Psp occurred earlier after radiotherapy completion and was associated with IDH1 R132H mutation, and MGMT methylation. In multivariate analysis, rCBV, rK2, and MGMT methylation status were independently associated with EP and Psp. All patients with a methylated MGMT promoter and a low rCBV (<1.75) were classified as Psp while all patients with an unmethylated MGMT promoter and a high rCBV (≥1.75) were classified as EP. Among patients with discordant MGMT methylation and rCBV characteristics, higher rK2 values tended to be associated with EP. ConclusionCombined analysis of MGMT methylation, rCBV and vessel permeability on K2 maps seems helpful to distinguish EP from Psp. A prospective study is warranted to confirm these results.

Multimodal Imaging of Nonenhancing Glioblastoma Regions.

Background:Clinical glioblastoma treatment mostly focuses on the contrast-enhancing tumor mass. Amino acid positron emission tomography (PET) can detect additional, nonenhancing glioblastoma-infiltrated brain regions that are difficult to distinguish on conventional magnetic resonance imaging (MRI). We combined MRI with perfusion imaging and amino acid PET to evaluate such nonenhancing glioblastoma regions.Methods:Structural MRI, relative cerebral blood volume (rCBV) maps from perfusion MRI, and α-[11C]-methyl-l-tryptophan (AMT)-PET images were analyzed in 20 patients with glioblastoma. The AMT uptake and rCBV (expressed as tumor to normal [T/N] ratios) were compared in nonenhancing tumor portions showing increased signal on T2/fluid-attenuated inversion recovery (T2/FLAIR) images.Results:Thirteen (65%) tumors showed robust heterogeneity in nonenhancing T2/FLAIR hyperintense areas on AMT-PET, whereas the nonenhancing regions in the remaining 7 cases had homogeneous AMT uptake (low in 6, high in 1). AMT and rCBV T/N ratios showed only a moderate correlation in the nonenhancing regions (r = 0.41, P = .017), but regions with very low rCBV (<0.79 T/N ratio) had invariably low AMT uptake.Conclusions:The findings demonstrate the metabolic and perfusion heterogeneity of nonenhancing T2/FLAIR hyperintense glioblastoma regions. Amino acid PET imaging of such regions can detect glioma-infiltrated brain for treatment targeting; however, very low rCBV values outside the contrast-enhancing tumor mass make increased AMT uptake in nonenhancing glioblastoma regions unlikely.

Evaluation of Response to Stereotactic Radiosurgery in Brain Metastases Using Multiparametric Magnetic Resonance Imaging and a Review of the Literature

AimsFollowing stereotactic radiosurgery (SRS), brain metastases initially increase in size in up to a third of cases, suggesting treatment failure. Current imaging using structural magnetic resonance imaging (MRI) cannot differentiate between tumour recurrence and SRS-induced changes, creating difficulties with patient management. Combining multiparametric MRI techniques, which assess tissue physiological and metabolic information, has shown promise in answering this clinical question. Materials and methodsMultiparametric MRI techniques, including spectroscopy, diffusion and perfusion imaging, were used for the differentiation of radiation-related changes and tumour recurrence after SRS for intracranial metastases in six cases. All patients presented with enlargement of the treated lesion, an increase in perilesional brain oedema and aggravation or appearance of neurological signs and symptoms from 7 to 29 weeks after primary treatment. ResultsMultiparametric imaging helped to differentiate features of tumour progression (n = 4) from radiation-related changes (n = 2). A low apparent diffusion coefficient (ADC) <1000 × 10−6 mm2/s, high relative cerebral blood volume (rCBV) ratio > 2.1, high choline:creatine (Cho:Cr) ratio > 1.8 suggested tumour recurrence. A high ADC > 1000 × 10−6 mm2/s, low rCBV ratio < 2.1, Cho:Cr ratio < 1.8 suggested SRS-induced radiation changes. Multiparametric MRI diagnosis was confirmed by histology or radiological and clinical follow-up. ConclusionMultiparametric MRI was helpful in the early identification of radiation-related changes and tumour recurrence and may be useful for monitoring treatment changes in intracranial neoplasms after SRS treatment.

Imaging prediction of isocitrate dehydrogenase (IDH) mutation in patients with glioma: a systemic review and meta-analysis.

To evaluate the imaging features of isocitrate dehydrogenase (IDH) mutant glioma and to assess the diagnostic performance of magnetic resonance imaging (MRI) for prediction of IDH mutation in patients with glioma. A systematic search of Ovid-MEDLINE and EMBASE up to 10 October 2017 was conducted to find relevant studies. The search terms combined synonyms for 'glioma', 'IDH mutation' and 'MRI'. Studies evaluating the imaging features of IDH mutant glioma and the diagnostic performance of MRI for prediction of IDH mutation in patients with glioma were selected. The pooled summary estimates of sensitivity and specificity and their 95% confidence intervals (CIs) were calculated using a bivariate random-effects model. The results of multiple subgroup analyses are reported. Twenty-eight original articles in a total of 2,146 patients with glioma were included. IDH mutant glioma showed frontal lobe predominance, less contrast enhancement, well-defined border, high apparent diffusion coefficient (ADC) value and low relative cerebral blood volume (rCBV) value. For the meta-analysis that included 18 original articles, the summary sensitivity was 86% (95% CI, 79%-91%) and the summary specificity was 87% (95% CI, 78-92%). In a subgroup analysis, the summary sensitivity of 2-hydroxyglutarate magnetic resonance spectroscopy (MRS) [96% (95% CI, 91-100%)] was higher than the summary sensitivities of other imaging modalities. IDH mutant glioma consistently demonstrated less aggressive imaging features than IDH wild-type glioma. Despite the variety of different MRI techniques used, MRI showed the potential to non-invasively predict IDH mutation in patients with glioma. 2-Hydroxyglutarate MRS shows higher pooled sensitivity than other imaging modalities. • IDH mutant glioma showed frontal lobe predominance, less contrast enhancement, well-defined border, high ADC value, and low rCBV value. • The diagnostic performance of MRI for prediction of IDH mutation in patients with glioma is within a clinically acceptable range, the summary sensitivity was 86% (95% CI, 79-91%) and the summary specificity was 87% (95% CI, 78-92%). • In a subgroup analysis, the summary sensitivity of 2-hydroxyglutarate MRS [96% (95% CI, 91-100%)] was higher than the summary sensitivities of other imaging modalities.

A New Technique for the Assessment of Cerebral Vasodilatory Capacity as Part of Catheter-Based Cerebral Angiography

Previous studies have demonstrated the value of cerebral vasodilatory capacity assessment for risk stratification in patients with extracranial arterial stenosis or occlusion. We describe a new method that assesses cerebral vasodilatory capacity as part of catheter-based cerebral angiography. We assessed regional cerebral blood volume (rCBV) in the arterial distribution of interest using a controlled contrast injection through a diagnostic catheter placed in the common carotid or the subclavian artery. rCBV maps were created using predefined algorithm based on contrast distribution in the venous phase (voxel size 0.466 mm3) into high, intermediate, low, and no detectable rCBV regions. rCBV maps were acquired again after the administration of intra-arterial nicardipine (1.5-2.5 mg), and percentage increases of the area of various grades of rCBV were calculated. Three patients with internal carotid artery stenosis (32% - 64% in severity) and 1 patient with extracranial vertebral artery stenosis (46% in severity) were assessed. There was a variable but consistent increase in the area of high rCBV in the ipsilateral hemisphere in 3 patients with internal carotid artery flow (5.5%-24.5%) and the cerebellum (9.6%) in 1 patient with vertebral artery flow assessments. The increase in high rCBV was most prominent in the patient who received 2.5 mg (24.5%) and least prominent in a patient who received 1.5 mg (5.5%) of intra-arterial nicardipine. There was a concurrent reduction in areas of intermediate and low rCBV (shift) in 3 patients, and there was an increase in all areas of rCBV grades (addition) in 1 patient. Selective assessment of cerebral vasodilatory response in the affected arterial distribution is feasible during catheter-based cerebral angiography.

Effects of Pretreatment Cerebral Blood Volume and Time to Recanalization on Clinical Outcomes in Endovascular Thrombectomy for Acute Ischemic Stroke

Faster time to recanalization leads to better clinical outcomes in patients treated with endovascular thrombectomy. Whether the association between time to recanalization and clinical outcomes depends on cerebral blood volume (CBV) obtained from pretreatment computed tomography (CT) perfusion (CTP) imaging was investigated. In consecutive patients with acute ischemic stroke who achieved recanalization by endovascular thrombectomy for intracranial internal carotid artery or M1 occlusion, the effects on clinical outcome of time to recanalization and the relative CBV value (rCBV) assessed by pretreatment CTP were evaluated. The patient population was divided into 2 groups according to rCBV: normal rCBV group (rCBV ≥ .9) and low rCBV group (rCBV < .9). In each group, time to recanalization was compared between the good and the poor clinical outcome groups. Sixty-four patients were eligible for this study. Twenty-six patients (40.6%) achieved good clinical outcomes. In the normal rCBV group, no association was found between clinical outcome and time to recanalization. In the low rCBV group, time to recanalization from CTP (101 minutes versus 136 minutes, P = .040) was significantly shorter in the good clinical outcome group. On binary logistic regression modeling, CTP to recanalization time (odds ratio 1.035 [1.004-1.067], P = .025) was an independent predictor of good clinical outcome only in the low rCBV group. The association between time to recanalization and clinical outcomes depends on rCBV obtained from pretreatment CTP. Time to recanalization is more important for good clinical outcomes in patients with low rCBV than in patients with normal rCBV.

Clinical applicability of and changes in perfusion MR imaging in brain metastases after stereotactic radiotherapy

To assess the applicability of perfusion-weighted (PWI) magnetic resonance (MR) imaging in clinical practice, as well as to evaluate the changes in PWI in brain metastases before and after stereotactic radiotherapy (SRT), and to correlate these changes to tumor status on conventional MR imaging. Serial MR images at baseline and at least 3 and 6 months after SRT were retrospectively evaluated. Size of metastases and the relative cerebral blood volume (rCBV), assessed with subjective visual inspection in the contrast enhanced area, were evaluated at each time point. Tumor behavior of metastases was categorized into four groups based on predefined changes on MRI during follow-up, or on histologically confirmed diagnosis; progressive disease (PD), pseudoprogression (PsPD), non-progressive disease (non-PD) and progression unspecified (PU). Twenty-six patients with 42 metastases were included. Fifteen percent (26/168) of all PW images could not be evaluated due to localization near large vessels or the scalp, presence of hemorrhage artefacts, and in 31% (52/168) due to unmeasurable residual metastases. The most common pattern (52%, 13/25 metastases) showed a high rCBV at baseline and low rCBV during follow-up, occurring in metastases with non-PD (23%, 3/13), PsPD (38%, 5/13) and PU (38%, 5/13). Including only metastases with a definite outcome generally showed low rCBV in PsPD or non-PD, and high rCBV in PD. Although non-PD and PsPD may be distinguished from PD after SRT using the PW images, the large proportion of images that could not be assessed due to artefacts and size severely hampers value of PWI in predicting tumor response after SRT.