The Impact of MRI-Based Advanced Neuroimaging on Neurooncologists' Clinical Decision-Making in Patients With Posttreatment High-Grade Glioma: A Prospective Survey-Based Study.

Background: Advanced MRI-based neuroimaging techniques, such as perfusion and spectroscopy, have been increasingly incorporated into routine follow-up protocols in patients treated for high-grade glioma (HGG), to help differentiate tumor progression from treatment effect. However, these techniques' influence on clinical management remains poorly understood. Objective: To evaluate the impact of MRI-based advanced neuroimaging on clinical decision-making in patients with HGG in the posttreatment setting. Methods: This prospective study, performed at a comprehensive cancer center from March 1, 2017, to October 31, 2020, included adult patients treated by chemoradiation for WHO grade 4 diffuse glioma who underwent MRIbased advanced neuroimaging (comprising multiple perfusion imaging sequences and spectroscopy) to further evaluate findings on conventional MRI equivocal for tumor progression versus treatment effect. The ordering neuro-oncologists completed surveys before and after each advanced neuroimaging session. The percent of care episodes with a change between the intended and actual management plan on the surveys conducted before and after advanced neuroimaging, respectively, was computed and compared with a previously published percent using the Wald test for independent samples proportions. Results: The study included 63 patients (mean age, 55±13 years; 36 women, 27 men) who underwent 70 advanced neuroimaging sessions. Ordering neuro-oncologists' intended and actual management plans on the surveys completed before and after advanced neuroimaging, respectively, differed in 44% (31/70, [95% CI: 33-56%]) of episodes, which differed from the previously published frequency of 8.5% (5/59) (p<.001). These management plan changes included selection of a different plan for 6/8 episodes with an intended plan to enroll patients in a clinical trial, 12/19 episodes with an intended plan to change chemotherapeutic agents, 4/8 episodes with an intended plan of surgical intervention, and 1/2 episodes with an intended plan of re-irradiation. The ordering neuro-oncologists found advanced neuroimaging to be helpful in 93% (95% CI: 87%-99%) (65/70) of episodes. Conclusion: Neuro-oncologists' management plans changed in a substantial fraction of adult patients with HGG who underwent advanced neuroimaging to further evaluate conventional MRI findings equivocal for tumor progression versus treatment effect. Clinical Impact: The findings support incorporation of advanced neuroimaging into HGG posttreatment monitoring protocols.

The utility of arterial spin labelled perfusion-weighted magnetic resonance imaging in measuring the vascularity of high grade gliomas - A prospective study.

Background: Dynamic susceptibility contrast (DSC) perfusion weighted imaging (PWI) currently remains the gold standard technique for measuring cerebral perfusion in glioma diagnosis and surveillance. Arterial spin labelling (ASL) PWI is a non-invasive alternative that does not require gadolinium contrast administration, although it is yet to be applied in widespread clinical practice. This study aims to assess the utility of measuring signal intensity in ASL PWI in predicting glioma vascularity by measuring maximal tumour signal intensity in patients based on pre-operative imaging and comparing this to maximal vessel density on histopathology. Methods: Pseudocontinuous ASL (pCASL) and DSC images were acquired pre-operatively in 21 patients with high grade gliomas. The maximal signal intensity within the gliomas over a region of interest of 100 mm2 was measured and also normalised to the contralateral cerebral cortex (nTBF-C), and cerebellum (nTBF-Cb). Maximal vessel density per 1 mm2 was determined on histopathology using CD31 and CD34 immunostaining on all participants. Results: Using ASL, statistically significant correlation was observed between maximal signal intensity (p < 0.05) and nTBF-C (p < 0.05) to maximal vessel density based on histopathology. Although a positive trend was also observed nTBF-Cb, this did not reach statistical significance. Using DSC, no statistically significant correlation was found between signal intensity, nTBF-C and nTBF-Cb. There was no correlation between maximal signal intensity between ASL and DSC. Average vessel density did not correlate with age, sex, previous treatment, or IDH status. Conclusions: ASL PWI imaging is a reliable marker of evaluating the vascularity of high grade gliomas and may be used as an adjunct to DSC PWI.

Location of Hyperintense Vessels on FLAIR Associated with the Location of Perfusion Deficits in PWI.

Perfusion imaging is preferred for identifying hypoperfusion in the management of acute ischemic stroke, but it is not always feasible/available. An alternative method for quantifying hypoperfusion, using FLAIR-hyperintense vessels (FHVs) in various vascular regions, has been proposed, with evidence of a statistical relationship with perfusion-weighted imaging (PWI) deficits and behavior. However, additional validation is needed to confirm that areas of suspected hypoperfusion (per the location of FHVs) correspond to the location of perfusion deficits in PWI. We examined the association between the location of FHVs and perfusion deficits in PWI in 101 individuals with acute ischemic stroke, prior to the receipt of reperfusion therapies. FHVs and PWI lesions were scored as present/absent in six vascular regions (i.e., the ACA, PCA, and (four sub-regions of) the MCA territories). Chi-square analyses showed a significant relationship between the two imaging techniques for five vascular regions (the relationship in the ACA territory was underpowered). These results suggest that for most areas of the brain, the general location of FHVs corresponds to hypoperfusion in those same vascular territories in PWI. In conjunction with prior work, results support the use of estimating the amount and location of hypoperfusion using FLAIR imaging when perfusion imaging is not available.

Perfusion magnetic resonance imaging in the differentiation between glioma recurrence and pseudoprogression: a systematic review, meta-analysis and meta-regression.

Background: Tumor recurrence and pseudoprogression (PsP) have similar imaging manifestations in conventional magnetic resonance imaging (MRI), although the subsequent treatments are completely different. This study aimed to evaluate the value of perfusion-weighted imaging (PWI) in differentiating PsP from glioma recurrence. Methods: A comprehensive literature search was performed to evaluate clinical studies focused on differentiating recurrent glioma from PsP using PWI, including dynamic susceptibility contrast MRI (DSC-MRI), dynamic contrast enhanced MRI (DCE-MRI), and arterial spin labeling (ASL). Study selection and data extraction were independently completed by two reviewers. The Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool was applied to evaluate the quality of the included studies. The software Stata 16.0 and Meta-Disc 1.4 were used for the meta-analysis. Meta-regression and subgroup analyses were applied to identify the sources of heterogeneity in the studies. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) prior to initiation (CRD42022304404). Results: A total of 40 studies were included, including 27 English studies and 13 Chinese studies. There were 1,341 patients with glioma recurrence and 876 patients with PsP. The pooled sensitivity and specificity of DSC-MRI for differentiating glioma recurrence from PsP were 0.82 [95% confidence interval (CI): 0.78 to 0.86] and 0.87 (95% CI: 0.80 to 0.92), respectively. The pooled sensitivity and specificity of DCE-MRI were 0.83 (95% CI: 0.76 to 0.89) and 0.83 (95% CI: 0.78 to 0.87), respectively. The pooled sensitivity and specificity of ASL were 0.80 (95% CI: 0.73 to 0.86) and 0.86 (95% CI: 0.76 to 0.92), respectively. Discussion: The DSC-MRI, DCE-MRI, and ASL perfusion techniques displayed high accuracy in distinguishing glioma recurrence from PsP, and DSC-MRI had a higher diagnostic performance than the other two techniques. However, due to the diversity of the parameters and threshold differences, further investigation and standardization are needed.

Dynamic susceptibility MR perfusion imaging of the brain: not a question of contrast agent molarity.

PURPOSE: Dynamic susceptibility contrast (DSC) perfusion-weighted MR imaging (PWI) is increasingly used in clinical neuroimaging for a range of conditions. More highly concentrated GBCAs (e.g., gadobutrol) are often preferred for DSC imaging because it is thought that more Gd is present in the volume of interest during first pass for a given equivalent injection rate. However, faster injection of a less viscous GBCA (e.g., gadoteridol) might generate a more compact and narrower contrast bolus thus obviating any perceived benefit of higher Gd concentration. This preliminary study aimed to analyze and compare DSC examinations in the healthy brain hemisphere of patients with brain tumors using gadobutrol and gadoteridol administered at injection rates of 4 and 6 mL/s. METHODS: Thirty-nine brain tumor patients studied with DSC-PWI were evaluated. A simplified gamma-variate model function was applied to calculate the mean peak, area under the curve (AUC), and full-width at half-maximum (FHWM) of concentration-time curves derived from ΔR2* signals at four different regions-of-interest (ROIs). Qualitative assessment of the derived CBV maps was also performed independently by 2 neuroradiologists. RESULTS: No qualitative or quantitative differences between the two GBCAs were observed when administered at a flow rate of 4 mL/s. At a flow rate of 6 mL/s, gadoteridol showed lower FWHM values. CONCLUSION: Gadobutrol and gadoteridol are equivalent for clinical assessment of qualitative CBV maps and quantitative perfusion parameters (FHWM) at a flow rate of 4 mL/s. At 6 mL/s, gadoteridol produces a narrower bolus shape and potentially improves quantitative assessment of perfusion parameters.

Predictive value of perfusion weighted imaging for early new lesions after stroke patients receive endovascular treatment.

BACKGROUND: Previous studies have focused on early new lesion-associated factors, but the differences in the perfusion status between the at-risk hypoperfusion areas with new lesions and the other hypoperfusion areas in stroke patients before thrombectomy is not clear. We investigated the value of perfusion-weighted imaging (PWI) in predicting early new lesions in patients after stroke. METHODS: Fifty-five acute stroke patients who underwent diffusion-weighted imaging (DWI) and PWI before and after thrombectomy within 24 h were eligible. The PWI parameters of the core infarct areas (high signal tissue on the DWI), the at-risk hypoperfusion areas (hypoperfusion area with new lesions at follow-up PWI) and the other hypoperfusion areas of patients with new lesions were collected. Statistical analysis was performed to predict new lesions after stroke. The differences in the PWI parameters of the core infarct areas, the at-risk hypoperfusion areas and the other hypoperfusion areas were compared. Receiver operating characteristic (ROC) curve analysis was used to assess the predictive value of the PWI parameters (P<0.05) for the occurrence of new lesions in patients with acute stroke after thrombectomy. RESULTS: Fifty-five stroke patients were analyzed, including forty patients (72.73%) with new lesions and fifteen patients (27.27%) without new lesions. Acute stroke patients with new lesions had a longer mean transit time (MTT) and time to peak (TTP) in the at-risk hypoperfusion areas (11.95±3.29; 38.30±11.39) than in the other hypoperfusion areas (8.68±2.08; 29.76±6.86), both of which were significantly different (P<0.0001; P<0.0001, respectively). The ROC analysis showed that the sensitivity and specificity of MTT for predicting the occurrence of new lesions after stroke were 70.00% and 87.50%, respectively; the sensitivity and specificity of TTP were 70.00% and 80.00%, respectively. CONCLUSIONS: MTT and TTP may be useful in predicting early new lesions in acute stroke patients after thrombectomy.

Cerebral Pulsed Arterial Spin Labeling Perfusion Weighted Imaging Predicts Language and Motor Outcomes in Neonatal Hypoxic-Ischemic Encephalopathy.

Rationale and Objectives: To compare cerebral pulsed arterial spin labeling (PASL) perfusion among controls, hypoxic ischemic encephalopathy (HIE) neonates with normal conventional MRI(HIE/MRI⊕), and HIE neonates with abnormal conventional MRI(HIE/MRI⊖). To create a predictive machine learning model of neurodevelopmental outcomes using cerebral PASL perfusion. Materials and Methods: A total of 73 full-term neonates were evaluated. The cerebral perfusion values were compared by permutation test to identify brain regions with significant perfusion changes among 18 controls, 40 HIE/MRI⊖ patients, and 15 HIE/MRI⊕ patients. A machine learning model was developed to predict neurodevelopmental outcomes using the averaged perfusion in those identified brain regions. Results: Significantly decreased PASL perfusion in HIE/MRI⊖ group, when compared with controls, were found in the anterior corona radiata, caudate, superior frontal gyrus, precentral gyrus. Both significantly increased and decreased cerebral perfusion changes were detected in HIE/MRI⊕ group, when compared with HIE/MRI⊖ group. There were no significant perfusion differences in the cerebellum, brainstem and deep structures of thalamus, putamen, and globus pallidus among the three groups. The machine learning model demonstrated significant correlation (p < 0.05) in predicting language(r = 0.48) and motor(r = 0.57) outcomes in HIE/MRI⊖ patients, and predicting language(r = 0.76), and motor(r = 0.53) outcomes in an additional group combining HIE/MRI⊖ and HIE/MRI⊕. Conclusion: Perfusion MRI can play an essential role in detecting HIE regardless of findings on conventional MRI and predicting language and motor outcomes in HIE survivors. The perfusion changes may also reveal important insights into the reperfusion response and intrinsic autoregulatory mechanisms. Our results suggest that perfusion imaging may be a useful adjunct to conventional MRI in the evaluation of HIE in clinical practice.

Differentiation Between True Tumor Progression of Glioblastoma and Pseudoprogression Using Diffusion-Weighted Imaging and Perfusion-Weighted Imaging: Systematic Review and Meta-analysis.

BACKGROUND: On brain magnetic resonance imaging, both diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI) are used to evaluate cerebral tumors. The purpose of this meta-analysis was to evaluate and compare the diagnostic performance of DWI and PWI in differentiating between pseudoprogression and true tumor progression of glioblastoma. METHODS: We performed a systematic review of the PubMed database from January 2000 to December 2019 for relevant studies. After application of specific inclusion and exclusion criteria, the eligible articles were evaluated for methodologic quality and risk of bias using the updated Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool. From the published study results, the pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio and their corresponding confidence intervals (% CI), and the area under the curve, were calculated individually for DWI and PWI. RESULTS: The meta-analysis included 24 studies, with a total of 900 patients. DWI was found to be slightly superior in terms of sensitivity and specificity, 0.88 (% CI 0.83-0.92) and 0.85 (% CI 0.78-0.91), respectively, compared with the respective values of PWI, 0.85 (% CI 0.81-0.89) and 0.79 (% CI 0.74-0.84). On comparison of the overall diagnostic accuracy of the MRI modalities using their respective area under the curve values (0.9156 for DWI, 0.9072 for PWI), no significant difference was demonstrated between the 2. CONCLUSIONS: Both DWI and PWI provided optimal diagnostic performance in differentiating pseudoprogression from true tumor progression in cerebral glioblastoma, and neither technique proved to be superior.

[Effects of "Tongdu Tiaoshen" acupuncture on cerebral blood flow in patients with high risk of cerebral ischemic stroke based on ASL and PWI technique].

OBJECTIVE: To observe the effects of "Tongdu Tiaoshen" acupuncture on cerebral blood flow in high-risk patients of cerebral ischemic stroke based on arterial spin labeling (ASL) and perfusion-weighted imaging (PWI), and to evaluate the clinical efficacy. METHODS: A total of 180 patients with transient ischemic attacks (TIA) / minor ischemic stroke (MIS) were randomly divided into an acupuncture A group, an acupuncture B group and a medication group, 60 cases in each group. The patients in the acupuncture A group were treated with "Tongdu Tiaoshen" acupuncture at Baihui (GV 20), Fengfu (GV 16), Yamen (GV 15), Dazhui (GV 14), Shenzhu (GV 12), Zhiyang (GV 9), Mingmen (GV 4), Yaoyangguan (GV 3) and Jingjiaji (EX-B 2), once a day; the patients in the acupuncture B group were treated with identical acupoints but was given once every other day; the patients in the medication group were treated with oral administration of nimodipine tablets, 30 mg, three times daily. All the three groups were treated for four weeks. ASL and PWI, including relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), relative mean transit time (rMTT) and relative time to peak (rTTP), were conducted before and after treatment; the changes of the test indexes were compared before and after treatment. The clinical efficacy of the three groups was compared. RESULTS: Compared before treatment, the numbers of ASL normal perfusion in the 3 groups were significantly increased after treatment (all P<0.01); the number of ASL normal perfusion in the acupuncture A group was higher than that in the acupuncture B group (P<0.05), but was not significantly different from that in the medication group (P>0.05). Compared before treatment, rCBV and rCBF in the 3 groups were significantly increased after treatment (all P<0.01), and rMTT and rTTP were significantly reduced (all P<0.01). After treatment, rCBV and rCBF in the acupuncture A group were higher than those in the acupuncture B group (all P<0.05); the rMTT and rTTP in the acupuncture A group were lower than those in the acupuncture B group (all P<0.05); the differences of PWI parameters after treatment were not statistically significant between the acupuncture A group and medication group (all P>0.05). The total effective rate was 88.3% (53/60) in the acupuncture A group, 73.3% (44/60) in the acupuncture B group and 90.0% (54/60) in the medication group; the total effective rate in the acupuncture A group was superior to that in the acupuncture B group (P<0.05), but was not significantly different from that in the medication group (P>0.05). CONCLUSION: "Tongdu Tiaoshen" acupuncture could effectively improve the hypoperfusion of cerebral blood flow in patients with high risk of cerebral ischemic stroke, reduce the incidence of severe CIS; acupuncture for once a day is better than once every other day.

Evaluation of Early Reperfusion Criteria in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Though still debated, early reperfusion is increasingly used as a biomarker for clinical outcome. However, the lack of a standard definition hinders the assessment of reperfusion therapies and study comparisons. The objective was to determine the optimal early reperfusion criteria that predicts clinical outcome in ischemic stroke. METHODS: Early reperfusion was assessed voxel-wise in 57 patients within 6 hours of symptom onset. The performance of the time to peak (TTP), the mean transit time (MTT), and the time to maximum of residue function (Tmax ) at various delays thresholds in predicting the neurological response (based on the National Institutes of Health Stroke Scale) and the functional outcome (modified Rankin scale ≤1) at 1 month were compared. A receiver operating characteristics (ROC) analysis determined the optimal extent of reperfusion. A novel unsupervised classification of reperfusion using group-based trajectory modeling (GBTM) was evaluated. RESULTS: MTT had a lower performance than TTP and Tmax in predicting the neurological response (P = .008 vs. TTP and P = .006 vs. Tmax ) or the functional outcome (P = .0006 vs. TTP; P = .002 vs. Tmax ). No delay threshold had a significantly higher predictive value than another. The optimal percentage of reperfusion was dependent on the outcome scale (P < .001). The GBTM-based classification of reperfusion was closely associated with the clinical outcome and had a similar accuracy compared to ROC-based classification. CONCLUSIONS: TTP and Tmax should be preferred to MTT in defining early reperfusion. GBTM provided a clinically relevant reperfusion classification that does not require prespecified delay thresholds or clinical outcomes.