Fluid-attenuated Inversion Recovery Volume Research Articles

Supramaximal Resection Can Prolong the Survival of Patients with Cortical Glioblastoma: A Volumetric Study.

We aimed to retrospectively determine the resection rate of fluid-attenuated inversion recovery (FLAIR) lesions to evaluate the clinical effects of supramaximal resection (SMR) on the survival of patients with glioblastoma (GBM). Thirty-three adults with newly diagnosed GBM who underwent gross total tumor resection were enrolled. The tumors were classified into cortical and deep-seated groups according to their contact with the cortical gray matter. Pre- and postoperative FLAIR and gadolinium-enhanced T1-weighted imaging tumor volumes were measured using a three-dimensional imaging volume analyzer, and the resection rate was calculated. To evaluate the association between SMR rate and outcome, we subdivided patients whose tumors were totally resected into the SMR and non-SMR groups by moving the threshold value of SMR in 10% increments from 0% and compared their overall survival (OS) change. An improvement in OS was observed when the threshold value of SMR was 30% or more. In the cortical group (n = 23), SMR (n = 8) tended to prolong OS compared with gross total resection (GTR) (n = 15), with the median OS of 69.6 and 22.1 months, respectively (p = 0.0945). Contrastingly, in the deep-seated group (n = 10), SMR (n = 4) significantly shortened OS compared with GTR (n = 6), with median OS of 10.2 and 27.9 months, respectively (p = 0.0221). SMR could help prolong OS in patients with cortical GBM when 30% or more volume reduction is achieved in FLAIR lesions, although the impact of SMR for deep-seated GBM must be validated in larger cohorts.

Synthesis of diffusion-weighted MRI scalar maps from FLAIR volumes using generative adversarial networks.

Acquisition and pre-processing pipelines for diffusion-weighted imaging (DWI) volumes are resource- and time-consuming. Generating synthetic DWI scalar maps from commonly acquired brain MRI sequences such as fluid-attenuated inversion recovery (FLAIR) could be useful for supplementing datasets. In this work we design and compare GAN-based image translation models for generating DWI scalar maps from FLAIR MRI for the first time. We evaluate a pix2pix model, two modified CycleGANs using paired and unpaired data, and a convolutional autoencoder in synthesizing DWI fractional anisotropy (FA) and mean diffusivity (MD) from whole FLAIR volumes. In total, 420 FLAIR and DWI volumes (11,957 images) from multi-center dementia and vascular disease cohorts were used for training/testing. Generated images were evaluated using two groups of metrics: (1) human perception metrics including peak signal-to-noise ratio (PSNR) and structural similarity (SSIM), (2) structural metrics including a newly proposed histogram similarity (Hist-KL) metric and mean squared error (MSE). Pix2pix demonstrated the best performance both quantitatively and qualitatively with mean PSNR, SSIM, and MSE metrics of 23.41 dB, 0.8, 0.004, respectively for MD generation, and 24.05 dB, 0.78, 0.004, respectively for FA generation. The new histogram similarity metric demonstrated sensitivity to differences in fine details between generated and real images with mean pix2pix MD and FA Hist-KL metrics of 11.73 and 3.74, respectively. Detailed analysis of clinically relevant regions of white matter (WM) and gray matter (GM) in the pix2pix images also showed strong significant (p < 0.001) correlations between real and synthetic FA values in both tissue types (R = 0.714 for GM, R = 0.877 for WM). Our results show that pix2pix's FA and MD models had significantly better structural similarity of tissue structures and fine details than other models, including WM tracts and CSF spaces, between real and generated images. Regional analysis of synthetic volumes showed that synthetic DWI images can not only be used to supplement clinical datasets, but demonstrates potential utility in bypassing or correcting registration in data pre-processing.

Alzheimer’s and vascular disease classification using regional texture biomarkers in FLAIR MRI

Interactions between subcortical vascular disease and dementia due to Alzheimer’s disease (AD) are unclear, and clinical overlap between the diseases makes diagnosis challenging. Existing studies have shown regional microstructural changes specific to each disease, and that textures in fluid-attenuated inversion recovery (FLAIR) MRI images may characterize abnormalities in tissue microstructure. This work aims to investigate regional FLAIR biomarkers that can differentiate dementia cohorts with and without subcortical vascular disease. FLAIR and diffusion MRI (dMRI) volumes were obtained in 65 mild cognitive impairment (MCI), 21 AD, 44 subcortical vascular MCI (scVMCI), 22 Mixed etiology, and 48 healthy elderly patients. FLAIR texture and intensity biomarkers were extracted from the normal appearing brain matter (NABM), WML penumbra, blood supply territory (BST), and white matter tract regions of each patient. All FLAIR biomarkers were correlated to dMRI metrics in each region and global WML load, and biomarker means between groups were compared using ANOVA. Binary classifications were performed using Random Forest classifiers to investigate the predictive nature of the regional biomarkers, and SHAP feature analysis was performed to further investigate optimal regions of interest for differentiating disease groups. The regional FLAIR biomarkers were strongly correlated to MD, while all biomarker regions but white matter tracts were strongly correlated to WML burden. Classification between Mixed disease and healthy, AD, and scVMCI patients yielded accuracies of 97%, 81%, and 72% respectively using WM tract biomarkers. Classification between scVMCI and healthy, MCI, and AD patients yielded accuracies of 89%, 84%, and 79% respectively using penumbra biomarkers. Only the classification between AD and healthy patients had optimal results using NABM biomarkers. This work presents novel regional FLAIR biomarkers that may quantify white matter degeneration related to subcortical vascular disease, and which indicate that investigating degeneration in specific regions may be more important than assessing global WML burden in vascular disease groups.

High-grade glioma imaging volumes and survival: a single-institution analysis of 101 patients after resection using intraoperative MRI.

Intraoperative magnetic resonance imaging (iMRI) has been efficacious in maximizing resection of high-grade gliomas (HGGs). In this single-institution study of patients with HGGs who underwent resection using iMRI, the authors present a volumetric-based survival analysis to evaluate progression-free survival (PFS) and overall survival (OS), as well as the impact of additional resection on survival. This retrospective analysis included patients with HGGs who underwent resection using iMRI from 2011 to 2021. Volumetric analyses of T1-weighted contrast-enhancing (T1W-CE), T2-weighted (T2W), and T2W fluid-attenuated inversion recovery (FLAIR) MRI sequences were assessed at preoperative, intraoperative, immediate postoperative, and three-month postoperative timepoints. Statistical analyses were carried out using log-rank and multivariable Cox proportional hazard regression analyses. A total of 101 patients (median age 57.0 years) were treated. In keeping with prior studies, statistically significant associations between greater EOR and longer PFS and OS were seen (p = 0.012 and p = 0.006, respectively). The results demonstrated significant associations of lower preoperative T2W, 3-month postoperative T2W, and 3-month postoperative FLAIR volumes with longer PFS and OS (p = 0.045 and p = 0.026, p = 0.031 and p = 0.006, p = 0.018 and p = 0.004, respectively), as well as associations between lower immediate postoperative T2W and immediate postoperative FLAIR volumes with longer OS (p = 0.002 and p = 0.02). There was no observed association in either PFS or OS for patients undergoing additional resection after initial iMRI scan (p = 0.387 and p = 0.592). This study of 101 patients with new or recurrent HGGs shows three-month postoperative T2W and FLAIR imaging volumes were significant prognosticators with respect to PFS and OS.

PATH-39. A 44-YEAR-OLD FEMALE WITH DICER1-MUTANT PRIMARY INTRACRANIAL SARCOMA WITH IMAGING NEAR END OF LIFE

Abstract DICER1-mutant intracranial sarcomas were recently defined by WHO in the 2021 CNS tumor classifications. Currently there is a lack of literature describing the clinical nature of this disease. Here we present a case of primary intracranial sarcoma with DICER1 mutation and unknown etiology. A 44-year-old female presented with aphasia and right-sided weakness. Clinical imaging confirmed the presence of a hemorrhagic mass in the left frontal lobe and superior falx. The patient underwent two surgical resections, but a clear diagnosis was difficult to make due to heterogenous histological features and inconclusive genomic testing. The surgical samples were sent to the National Institute of Health where genetic testing indicated a DICER1 E1813D mutation with high allele frequency (97%), a TP53 mutation with high allele frequency (95%), and a high variant allele frequency NF1 splice site mutation (96%). This resulted in a diagnosis of DICER1-mutant primary intracranial sarcoma. The patient was treated with temozolomide, bevacizumab, and CPT-11. 382 days after the mass was originally identified, the patient died. A detailed analysis of the radiographic images was performed by creating T1-weighted post-contrast enhancement maps (T1C) and T2-weighted fluid attenuated inversion recovery (FLAIR) hyper-intensity maps for each timepoint. We plotted these volumes over time alongside the patient’s treatment history. Large spikes in T1C and FLAIR volume were seen 4 days prior to initiation of temozolomide and 31 days after CPT-11 treatment was ended. At the final clinical MRI, both volumes were about 4 times greater than that of the initial scan. Despite this disease’s aggressive nature, it can be difficult to accurately diagnose, due in part to very few studies investigating the clinical features of this rare tumor. With the addition of this diagnosis to WHO CNS5, future studies should examine the behavior of these tumors, aiding in earlier diagnosis and improvement of treatment guidance.

Bevacizumab for Cerebral Radionecrosis: A Single-Center Experience.

Cerebral radionecrosis, a subacute or late effect of radiotherapy, can be debilitating and difficult to treat. Steroids can reduce symptoms, but have significant long-term side effects. Bevacizumab has been shown to reduce edema and other radiologic features associated with radionecrosis and improve patient symptoms. We report our experience using bevacizumab for cerebral radionecrosis. We retrospectively reviewed the charts of all patients treated at our institution with bevacizumab for non-glioma-associated cerebral radionecrosis. We recorded change in symptoms, change in steroids, change in performance status, time to tumor progression, and time to death. We delineated the volume of necrosis pre- and post-bevacizumab on T1-post-gadolinium and fluid-attenuated inversion recovery (FLAIR) MRI scans. We identified 15 patients, 8 with brain metastases, 6 with meningioma, and 1 with nasopharyngeal carcinoma. Most received four doses of bevacizumab, 7.5 mg/kg q 3 weeks × 4 doses. Neuroimaging demonstrated a reduced T1 gadolinium-enhancing volume and edema in 14/15 patients (the average reduction in T1-post-gadolinium volume was 3.0 cm3, and average reduction in FLAIR volume was 27.9 cm3). There was no appreciable change in patient performance status. Steroid doses decreased in five of nine patients. There was a high rate (26%) of adverse events, including pulmonary embolism, stroke, and wound dehiscence. The median progression-free survival was 6.5 months. Although bevacizumab is commonly prescribed for cerebral radionecrosis, in our retrospective cohort, the clinical benefits were modest and there was significant toxicity.

Early volumetric, perfusion, and diffusion MRI changes after mutant isocitrate dehydrogenase (IDH) inhibitor treatment in IDH1-mutant gliomas.

BackgroundInhibition of the isocitrate dehydrogenase (IDH)-mutant enzyme is a novel therapeutic target in IDH-mutant gliomas. Imaging biomarkers of IDH inhibitor treatment efficacy in human IDH-mutant gliomas are largely unknown. This study investigated early volumetric, perfusion, and diffusion MRI changes in IDH1-mutant gliomas during IDH inhibitor treatment.MethodsTwenty-nine IDH1-mutant glioma patients who received IDH inhibitor and obtained anatomical, perfusion, and diffusion MRI pretreatment at 3–6 weeks (n = 23) and/or 2–4 months (n = 14) of treatment were retrospectively studied. Normalized relative cerebral blood volume (nrCBV), apparent diffusion coefficient (ADC), and fluid-attenuated inversion recovery (FLAIR) hyperintensity volume were analyzed.ResultsAfter 3–6 weeks of treatment, nrCBV was significantly increased (P = .004; mean %change = 24.15%) but not FLAIR volume (P = .23; mean %change = 11.05%) or ADC (P = .52; mean %change = -1.77%). Associations between shorter progression-free survival (PFS) with posttreatment nrCBV > 1.55 (P = .05; median PFS, 240 vs 55 days) and increased FLAIR volume > 4 cm3 (P = .06; 227 vs 29 days) trended toward significance. After 2–4 months, nrCBV, FLAIR volume, and ADC were not significantly different from baseline, but an nrCBV increase > 0% (P = .002; 1121 vs 257 days), posttreatment nrCBV > 1.8 (P = .01; 1121 vs. 270 days), posttreatment ADC < 1.15 μm2/ms (P = .02; 421 vs 215 days), median nrCBV/ADC ratio increase > 0% (P = .02; 1121 vs 270 days), and FLAIR volume change > 4 cm3 (P = .03; 421 vs 226.5 days) were associated with shorter PFS.ConclusionsIncreased nrCBV at 3–6 weeks of treatment may reflect transient therapeutic and/or tumor growth changes, whereas nrCBV, ADC, and FLAIR volume changes occurring at 2–4 months of treatment may more accurately reflect antitumor response to IDH inhibition.

Case Report: End-Stage Recurrent Glioblastoma Treated With a New Noninvasive Non-Contact Oncomagnetic Device.

Alternating electric field therapy has been approved for glioblastoma (GBM). We have preclinical evidence for anticancer effects in GBM cell cultures and mouse xenografts with an oscillating magnetic field (OMF) generating device. Here we report OMF treatment of end-stage recurrent glioblastoma in a 53-year-old man who had undergone radical surgical excision and chemoradiotherapy, and experimental gene therapy for a left frontal tumor. He experienced tumor recurrence and progressive enlargement with leptomeningeal involvement. OMF for 5 weeks was well tolerated, with 31% reduction of contrast-enhanced tumor volume and reduction in abnormal T2-weighted Fluid-Attenuated Inversion Recovery volume. Tumor shrinkage appeared to correlate with treatment dose. These findings suggest a powerful new noninvasive therapy for glioblastoma.

Randomized clinical trial comparing a rivaroxaban-based with an antiplatelet-based strategy for cerebral embolization after TAVR (EARTH TAVR)-a magnetic resonance imaging substudy of the GALILEO trial

Abstract Background Cerebral embolization in patients after Transcatheter Aortic Valve Replacement (TAVR) represents a serious complication, that was related to impaired bioprosthetic leaflet motion and new-onset atrial fibrillation (AFib). Purpose Hereafter we present the first randomized study comparing the effect of an anticoagulation plus antiplatelet with a dual antiplatelet antithrombotic treatment in patients after TAVR on cerebral embolizations as assessed by serial cerebral magnetic resonance imaging (MRI). Methods The Evaluation of Cerebral Thrombembolism After TAVR (EARTH - TAVR) study was conducted as an investigator initiated substudy of the multicenter, randomized, GALILEO study. After successful TAVR, patients without indication for chronic anticoagulation were randomly assigned to rivaroxaban 10mg plus acetylsalicylic acid 75–100mg once-daily or clopidogrel 75mg plus acetylsalicylic acid 75–100mg once-daily. Cerebral MRI scans were performed pre-TAVR as a baseline, post-TAVR (within 24–48 hours after TAVR) and 90 days after TAVR. The MRI protocol included diffusion-weighted (DWI) and fluid-attenuated inversion recovery (FLAIR) imaging. Cerebral embolic lesions were evaluated by an independent cerebral MRI core lab. The primary outcome measure of this study was the occurrence and extent of cerebral embolizations as measured by total volume of new ischaemic cerebral lesions. Results 36 patients were enrolled in the EARTH and the GALILEO study. The DWI MRI scans revealed an increase of cerebral lesions and volume post-TAVR by a median of 4.75 (95% NBCI 2.1–8.9) and 0.26cm3 (95% NBCI 0.11–0.59). On FLAIR imaging, lesion number and volume increased by a median of 3 (95% NBCI 1.5–6) and 0.1 cm3 (95% NBCI 0.04–0.31). At the 90 days MRI scan, there was no statistically significant change in cerebral lesions, if compared to the post-TAVR scan, irrespective of the treatment arm. Conclusion Thromboembolic events occur largely in the periinterventional phase post TAVR. Thereafter, the risk for additional cerebral embolization is low. An additional rivaroxaban therapy beyond antiplatelet inhibition did not impact on cerebral thromboembolism. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bayer Pharmaceuticals

Long-term effectiveness of natalizumab on MRI outcomes and no evidence of disease activity in relapsing-remitting multiple sclerosis patients treated in a Czech Republic real-world setting: A longitudinal, retrospective study

BackgroundMagnetic resonance imaging (MRI) data from multiple sclerosis (MS) patients treated in real-world settings are important for understanding disease-modifying therapy effects, including no evidence of disease activity (NEDA) assessment. This longitudinal, retrospective, single-cohort analysis assessed MRI and clinical disease outcomes in patients with relapsing-remitting MS treated with natalizumab for up to 5 years in Prague, the Czech Republic. MethodsThe primary study endpoint was the proportion of patients free of new or enlarging fluid-attenuated inversion recovery (FLAIR) lesions after at least 2 years of natalizumab treatment. Secondary endpoints included percentage brain volume change over time, the number of new T1-hypointense lesions that persisted for ≥6 months, FLAIR and T1-hypointense lesion volume change over time, and the proportion of patients with NEDA-3 (defined as no relapses, no confirmed disability worsening, and no new or enlarging FLAIR lesions). ResultsA total of 193 patients were included in the study. During year 1 of natalizumab treatment, 78.9% of patients had no new or enlarging FLAIR lesions and 79.5% had no new T1 lesions. These proportions increased in years 2–5, with ≥98.0% of patients free of new or enlarging FLAIR lesions and ≥98.8% free of new T1 lesions. During year 1 on natalizumab, 52.2% of patients achieved NEDA-3; this proportion increased to ≥69.2% in years 2–5. ConclusionThis study provides additional evidence that long-term MS disease activity, as measured by both MRI activity and NEDA-3, is well-controlled in patients treated with natalizumab in real-world settings.

Eyebrow supraorbital keyhole craniotomy for olfactory groove meningiomas with endoscope assistance: case series and systematic review of extent of resection, quantification of postoperative frontal lobe injury, anosmia, and recurrence.

Olfactory groove meningiomas (OGMs) are commonly treated with open craniotomy. Endonasal approaches have also been described. To present clinical and radiographic outcomes for the minimally invasive eyebrow incision supraorbital keyhole approach with endoscopic assistance for OGMs. We performed a retrospective single-center cohort study and a systematic literature review. Fifteen patients were identified, all with Grade I meningiomas. Radiographic gross total resection of enhancing tumor was achieved in all patients. Mean frontal lobe fluid-attenuated inversion recovery volume decreased from 11.1 ± 18.3cm3 preoperatively to 9.9 ± 11.4cm3 immediately postoperatively, and there was minimal new restricted diffusion (3.2 ± 2.2cm3; max 7.5cm3). Median length of stay was 3days (range 2-8). Vision was improved in 4 (80%) and stable in 1 (20%) of 5 patients with a preoperative deficit. New postoperative anosmia occurred in 3 (23%) of 13 patients with any preoperative olfaction. All patients were satisfied with their cosmetic result at 3months. After a median follow-up of 32.2months, there were 2 (13.3%) asymptomatic radiographic recurrences, 1 treated with radiosurgery and the other with endoscopic endonasal approach (EEA). No patients required further craniotomy. Systematic review revealed the present series to be the largest to date reporting disaggregated outcomes for the eyebrow approach to OGM. The eyebrow incision supraorbital keyhole craniotomy with endoscopic assistance is a safe and effective approach to OGM with tumor control rates similar to more invasive open approaches and better than the endonasal approach. Rates of frontal lobe injury, CSF leak and anosmia are comparatively low.

Matrix Metalloproteinase-9 Relationship With Infarct Growth and Hemorrhagic Transformation in the Era of Thrombectomy.

Objective: To assess the relationship between matrix metalloproteinase 9 (MMP-9), a proteolytic enzyme involved in the breakdown of the blood-brain barrier, and infarct growth and hemorrhagic transformation in acute ischemic stroke (AIS) with large vessel occlusion (LVO) in the era of mechanical thrombectomy (MT) using the kinetics of MMP-9 and sequential magnetic resonance imaging (MRI).Methods: HIBISCUS-STROKE is a cohort study including AIS patients with LVO treated with MT following admission MRI. Patients underwent sequential assessment of MMP-9, follow-up CT at day 1, and MRI at day 6. The CT scan at day 1 classified any hemorrhagic transformation according to the European Co-operative Acute Stroke Study-II (ECASS II) classification. Infarct growth was defined as the difference between final Fluid-Attenuated Inversion Recovery volume and baseline diffusion-weighted imaging volume. Conditional logistic regression analyses were adjusted for main confounding variables including reperfusion status.Results: One hundred and forty-eight patients represent the study population. A high MMP-9 level at 6 h from admission (H6) (p = 0.02), a high glucose level (p = 0.01), a high temperature (p = 0.04), and lack of reperfusion (p = 0.02) were associated with infarct growth. A high MMP-9 level at H6 (p = 0.03), a high glucose level (p = 0.03) and a long delay from symptom onset to groin puncture (p = 0.01) were associated with hemorrhagic transformation.Conclusions: In this MT cohort study, MMP-9 level at H6 predicts infarct growth and hemorrhagic transformation.

Risk HLA-DRB1 alleles differentially influence brain and lesion volumes in Japanese patients with multiple sclerosis

BackgroundThe effects of distinct HLA alleles on the brain and lesion volumes remain to be established, particularly in non-Caucasian populations. Two distinct susceptibility alleles, DRB1*15:01 and DRB1*04:05, are prevalent in the Japanese population; we therefore aimed to clarify the effects of HLA-DRB1 alleles on brain and lesion volumes in multiple sclerosis (MS). MethodsA total of 66 patients with MS (50 relapsing remitting, 16 progressive) underwent brain MRI volumetry measuring fluid-attenuated inversion recovery (FLAIR) and T1 lesion volumes, and normalized whole-brain (NWBV), white matter (NWMV), gray matter (NGMV), cortical gray matter (NCGMV), deep gray matter (NDGMV) and thalamus (NTV) volumes, and HLA-DRB1 genotyping. ResultsCarriers of HLA-DRB1*15:01(+)*04:05(−) and HLA-DRB1*15:01(−)*04:05(+) comprised 25.8% and 31.8% of patients, respectively. HLA-DRB1*15:01 carriers showed negative correlations between disease duration and NWBV (rs = −0.484, p = .036), NWMV (rs = −0.593, p = .008), and NTV (rs = −0.572, p = .011), and positive correlations between disease duration and FLAIR (rs = 0.539, p = .017) and T1 lesion volumes (rs = 0.545, p = .016). By contrast, no significant correlation of any MRI parameters with disease duration was found in HLA-DRB1*04:05 carriers. HLA-DRB1*15:01 carriers had a significantly faster reduction in NWBV and NWMV by disease duration and smaller NDGMV than DRB1*15:01 non-carriers, whereas HLA-DRB1*04:05 carriers had a significantly slower increase in FLAIR and T1 lesion volumes than HLA-DRB1*04:05 non-carriers. ConclusionsOur study suggests that distinct HLA-DRB1 alleles could differentially influence brain and lesion volumes over the disease course of MS.

Pathology-preserving intensity standardization framework for multi-institutional FLAIR MRI datasets

Fluid-Attenuated Inversion Recovery (FLAIR) MRI are used by physicians to analyze white matter lesions (WML) of the brain, which are related to neurodegenerative diseases such as dementia and vascular disease. To study the causes and progression of these diseases, multi-centre (MC) studies are conducted, with images acquired and analyzed from multiple institutions. Due to differences in acquisition software and hardware, there is variability in image properties, which creates challenges for automated algorithms. This work explores this variability, known as the MC effect, by analyzing nearly 5000 MC FLAIR volumes and proposes an intensity standardization framework to normalize intensity non-standardness in FLAIR MRI, while ensuring the appearance of WML. Results show that original image characteristics varied significantly between scanner vendors and centres, and that this variability was reduced with standardization. To further highlight the utility of intensity standardization, a threshold-based brain extraction algorithm is implemented and compared with a classifier-based approach. A competitive Dice Similarity Coefficient of 81% was achieved on 183 volumes, demonstrating that optimized pre-processing can effectively reduce the variability in MC studies, allowing for simplified algorithms to be applied on large datasets robustly.

Extending the resection beyond the contrast-enhancement for glioblastoma: feasibility, efficacy, and outcomes

Object: It is becoming well-established that increasing extent of resection with decreasing residual volume is associated with delayed recurrence and prolonged survival for patients with glioblastoma (GBM). These prior studies are based on evaluating the contrast-enhancing (CE) tumour and not the surrounding fluid attenuated inversion recovery (FLAIR) volume. It therefore remains unclear if the resection beyond the CE portion of the tumour if it translates into improved outcomes for patients with GBM.Methods: Adult patients who underwent resection of a primary glioblastoma at a tertiary care institution between January 1, 2007 and December 31, 2012 and underwent radiation and temozolomide chemotherapy were retrospectively reviewed. Pre and postoperative MRI images were measured for CE tumour and FLAIR volumes. Multivariate proportional hazards were used to assess associations with both time to recurrence and death. Values with p < 0.05 were considered statistically significant.Results: 245 patients met the inclusion criteria. The median [IQR] preoperative CE and FLAIR tumour volumes were 31.9 [13.9–56.1] cm3 and 78.3 [44.7–115.6] cm3, respectively. Following surgery, the median [IQR] postoperative CE and FLAIR tumour volumes were 1.9 [0–7.1] cm3 and 59.7 [29.7–94.2] cm3, respectively. In multivariate analyses, the postoperative FLAIR volume was not associated with recurrence and/or survival (p > 0.05). However, the postoperative CE tumour volume was significantly associated with both recurrence [HR (95%CI); 1.026 (1.005–1.048), p = 0.01] and survival [HR (95%CI); 1.027 (1.007–1.032), p = 0.001]. The postoperative FLAIR volume was also not associated with recurrence and/or survival among patients who underwent gross total resection of the CE portion of the tumour as well as those who underwent supratotal resection.Conclusions: In this study, the volume of CE tumour remaining after resection is more important than FLAIR volume in regards to recurrence and survival for patients with GBM.

Volumetric response of progressing post-SRS lesions treated with laser interstitial thermal therapy.

We analyzed volumetric response of metastatic brain tumors that progressed despite treatment with stereotactic radiosurgery (SRS) after treatment with laser interstitial thermal therapy (LITT). We retrospectively reviewed consecutive patients treated from 1/2012 to 10/2015 with LITT for metastatic brain tumors demonstrating progression after SRS. Volumes were quantified using MRI with contrast-enhanced T1-weighted (T1W) and fluid-attenuated inversion recovery (FLAIR). Fifty lesions from 36 patients were studied. Lesions were assessed prior to LITT, immediately after LITT, 0-90 days after LITT, 90-180 days after LITT, 180-270 days after LITT, and 270-360 days after LITT. The median T1W volume was 5.05cc (range 0.54-23.31cc) before LITT treatment (n = 50), 7.70cc (range 1.72-38.76cc) 0-90 days after LITT (n = 47), and 3.68cc (range 1.282-48.31cc) 180-270 days after LITT (n = 21). The median FLAIR volume was 43.36cc (range 3.09-233.01cc) before LITT treatment (n = 50), 37.13cc (range 3.48-244.23cc) 0-90 days after LITT (n = 43), 31.68cc (range 1.6-248.75cc) 180-270 days after LITT (n = 18). The 6-month FLAIR volume showed a statistically significant reduction compared to pretreatment (p = 0.04). After selecting for cases where patients had two or more post-operative MRIs, we found that 24 lesions (63%) demonstrated an overall downward trend and 14 lesions (37%) demonstrated an upward trend. The median pre-treatment T1W volume for the patients whose lesions demonstrated volumetric reduction after LITT was 3.54cc (range 0.539-10.06cc) and for those who did not demonstrate volumetric reduction after LITT it was 8.81cc (range 0.926-23.313cc). The pre-treatment tumor volume plays a significant role in determining response to LITT with smaller tumor volumes responding better to LITT than tumors with larger volumes.

Monitoring Radiation Treatment Effects in Glioblastoma: FLAIR Volume as Significant Predictor of Survival.

Glioblastoma is the most common adult central nervous system malignancy and carries a poor prognosis. Disease progression and recurrence after chemoradiotherapy are assessed via serial magnetic resonance imaging sequences. T2-weighted fluid-attenuated inversion recovery (FLAIR) signal is presumed to represent edema containing microscopic cancer infiltration. Here we assessed the prognostic impact of computerized volumetry of FLAIR signal in the peri-treatment setting for glioblastoma. We analyzed pre- and posttreatment FLAIR sequences of 40 patients treated at the Columbia University Medical Center between 2011 and 2014, excluding those without high-quality FLAIR imaging within 2 weeks before treatment and 60 to 180 days afterward. We manually contoured regions of FLAIR hyperintensity as per Radiation Therapy Oncology Group guidelines and calculated the volumes of nonenhancing tumor burden. At the time of this study, all but 1 patient had died. Pre- and posttreatment FLAIR volumes were assessed for correlation to overall and progression-free survival. Larger post-treatment FLAIR volumes from sequences taken between 60 and 180 days after conclusion of chemoradiotherapy were negatively correlated with overall survival (P = .048 on Pearson's correlation and P = .017 and P = .043 on univariable and multivariable Cox regression analyses, respectively) and progression-free survival (P = .002 on Pearson's correlation and P = < .001 and P = < .001 on univariable and multivariable Cox regression analyses). This study suggests that higher FLAIR volumes in the 2- to 6-month posttreatment window are associated with worsened survival.

Dynamics of FLAIR Volume Changes in Glioblastoma and Prediction of Survival.

The extent of tumor resection (EOTR) calculated by enhanced T1 changes in glioblastomas has been previously reported to predict survival. However, fluid-attenuated inversion recovery (FLAIR) volume may better represent tumor burden. In this study, we report the first assessment of the dynamics of FLAIR volume changes over time as a predictive variable for post-resection overall survival (OS). Contemporary data from 103 consecutive patients with complete imaging and clinical data who underwent resection of newly diagnosed glioblastoma followed by the Stupp protocol between 2010 and 2013 were analyzed. Clinical, radiographic, and outcome parameters were retrieved for each patient, including magnetic resonance imaging (MRI)-based volumetric tumor analysis before, immediately after, and 3months post-surgery. OS rate was 17.6months. A significant incremental OS advantage was noted, with as little as 85% T1-weighted gadolinium-enhanced (T1Gd)-EOTR measured on contrast-enhanced MRI. Pre- and immediate postoperative FLAIR-based EOTR was not predictive of OS; however, abnormal FLAIR volume measured 3months post-surgery correlated significantly with outcome when FLAIR residual tumor volume (RTV) was <19.3cm3 and <46% of baseline volume (p<0.0001 for both). Age and isocitrate dehydrogenase (IDH)-1 mutation were predictive of OS (p<0.0001, Cox proportional hazards). OS correlated with the immediate postoperative T1Gd-EOTR measured by enhanced T1 MRI, but not by FLAIR volume. Diminished abnormal FLAIR volume at 3months post-surgery was associated with OS benefit when FLAIR-RTV was <19.3cm3 or <46% of baseline. These threshold values provide a new radiological variable that can be used for prediction of OS in patients with glioblastoma immediately after completion of standard chemoradiation.

Volumetric relationship between 2-hydroxyglutarate and FLAIR hyperintensity has potential implications for radiotherapy planning of mutant IDH glioma patients.

Gliomas with mutant isocitrate dehydrogenase (IDH) produce high levels of 2-hydroxyglutarate (2HG) that can be quantitatively measured by 3D magnetic resonance spectroscopic imaging (MRSI). Current glioma MRI primarily relies upon fluid-attenuated inversion recovery (FLAIR) hyperintensity for treatment planning, although this lacks specificity for tumor cells. Here, we investigated the relationship between 2HG and FLAIR in mutant IDH glioma patients to determine whether 2HG mapping is valuable for radiotherapy planning. Seventeen patients with mutant IDH1 gliomas were imaged by 3 T MRI. A 3D MRSI sequence was employed to specifically image 2HG. FLAIR imaging was performed using standard clinical protocol. Regions of interest (ROIs) were determined for FLAIR and optimally thresholded 2HG hyperintensities. The overlap, displacement, and volumes of 2HG and FLAIR ROIs were calculated. In 8 of 17 (47%) patients, the 2HG volume was larger than FLAIR volume. Across the entire cohort, the mean volume of 2HG was 35.3 cc (range, 5.3-92.7 cc), while the mean volume of FLAIR was 35.8 cc (range, 6.3-140.8 cc). FLAIR and 2HG ROIs had mean overlap of 0.28 (Dice coefficients range, 0.03-0.57) and mean displacement of 12.2 mm (range, 3.2-23.5 mm) between their centers of mass. Our results indicate that for a substantial number of patients, the 2HG volumetric assessment of tumor burden is more extensive than FLAIR volume. In addition, there is only partial overlap and asymmetric displacement between the centers of FLAIR and 2HG ROIs. These results may have important implications for radiotherapy planning of IDH mutant glioma.

Restriction spectrum imaging predicts response to bevacizumab in patients with high-grade glioma.

Diffusion-weighted imaging has shown initial promise for evaluating response to bevacizumab in patients with high-grade glioma (HGG). However, it is well recognized that the apparent diffusion coefficient (ADC) is influenced by bevacizumab-induced reductions in edema, which may limit its prognostic value. We demonstrate that an advanced diffusion-weighted imaging technique, restriction spectrum imaging (RSI), improves the evaluation of response to bevacizumab because unlike ADC, RSI is not affected by resolution of edema. RSI and ADC maps were analyzed for 40 patients with HGG prior to and following initiation of bevacizumab. Volumes of interest were drawn for regions of contrast enhancement (CE) and fluid attenuated inversion recovery (FLAIR) hyperintensity and histogram percentiles within volumes of interest were calculated for ADC 10th percentile (ADC-CE10%, ADC-FLAIR10%) and for RSI 90th percentile (RSI-CE90%, RSI-FLAIR90%). Cox proportional hazard models were used to evaluate the relationship between imaging parameters, progression-free survival (PFS), and overall survival (OS). An increase in RSI-FLAIR90% following bevacizumab was the strongest predictor of poor PFS (P= .016) and OS (P= .004), whereas decreases in ADC-FLAIR10% showed a weaker association with OS only (P= .041). Within the CE region, increases in RSI-CE90% alone were associated with poorer OS. Correlational analysis revealed that decreases in FLAIR volume were associated with decreases in ADC-FLAIR10%, but not with changes in RSI-FLAIR90%. RSI is less influenced by changes in edema, conferring an advantage of RSI over ADC for evaluating response to anti-angiogenic therapy in patients with HGG.