Qualitative Assessment of Advanced MRI in Post-Treatment High Grade Gliomas Follow Up: Do We Agree?

PURPOSE: MRI is commonly used in follow up of high grade glioma. Our purpose is to assess the interrater agreement on the increasingly used visual qualitative assessment of various conventional and advanced MR techniques in the setting of treated high grade glioma in comparison to the well established quantitative measurements. METHODS: We prospectively enrolled HGG patients who underwent reresection of a new enhancing lesion on post-treatment 3T MR examination including DWI, DCE and DSC sequences. Two neuroradiologists objectively assessed the diffusion and perfusion maps by placing ROI on representative post-processed maps. They subjectively assessed the post-contrast, perfusion and diffusion sequences. Interrater agreement and concordance correlation coefficient were calculated. RESULTS: Twenty-eight lesions were included. The interrater agreement on the qualitative assessment was good for k-trans (k = 0.73), moderate for Vp (k = 0.52), fair for AUC and Ve maps (k = 0.37 and 0.21), fair for corrected CBV (k = 0.39) and poor for the enhancement pattern and presence of diffusion restriction (k = 0.02 and 0.07). The concordance between the quantitative measurements was substantial for AUC and Vp (ρc = 0.98 and 0.97), moderate for k-trans and corrected CBV (ρc = 0.94) and poor for Ve and ADC (ρc = 0.86 and 0.24). CONCLUSION: While the quantitative measurements of DSC and DCE perfusion maps show satisfactory inter-rater agreement, the qualitative assessment has lower interobserver agreement and should not be relied upon solely in the interpretation. Similarly, the suboptimal inter-rater agreement on the interpretation of enhancement pattern and diffusion restriction potentially limits their usefulness in differentiating glioma recurrence from treatment related changes.

Preoperative Determination of Isocitrate Dehydrogenase Mutation in Gliomas Using Spectral Editing MRS: A Prospective Study.

BACKGROUND: The edited magnetic resonance spectroscopy (MRS) technique has not yet been formally evaluated for the in vivo detection of 2-hydroxyglutarate (2-HG) in patients with gliomas of various grades. PURPOSE: To evaluate the diagnostic accuracy of edited MRS in the preoperative identification of the isocitrate dehydrogenase (IDH) mutation status in patients with gliomas. STUDY TYPE: Prospective. POPULATION: Fifty-eight subjects (31 glioblastomas, 27 grade II and III gliomas). FIELD STRENGTH/SEQUENCE: Mescher-Garwood (MEGA)-PRESS and routine clinical brain tumor MR sequences were used at 3T. ASSESSMENT: Data were analyzed using an advanced method for accurate, robust, and efficient spectral fitting (AMARES) from jMRUI software. The amplitudes of the 2-HG, N-acetyl-aspartate (NAA), choline (Cho), and creatine/phosphocreatine (Cr) resonances were calculated with their associated Cramer-Rao lower bound (CRLB). The IDH1 R132H mutation status was assessed by immunohistochemistry for all patients. Patients with grades II and III gliomas with negative immunohistochemistry underwent DNA sequencing to further interrogate IDH mutation status. STATISTICAL TEST: The differences in 2-HG amplitudes, 2-HG/NAA, 2-HG/Cho, and 2-HG/Cr between IDH-mutant and IDH-wildtype gliomas were assessed using Mann-Whitney U-tests. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic accuracy of each parameter. RESULTS: The 2-HG amplitudes, 2-HG/NAA, and 2-HG/Cho were higher for IDH-mutant gliomas than IDH-wildtype gliomas (P < 0.007). Using a CRLB threshold <30%, a 2-HG cutoff greater than 0 had a sensitivity of 80% (95% confidence interval [CI]: 52-96%) and a specificity of 81% (95% CI: 54-96%) in identifying IDH-mutant gliomas. In the subset of patients with grades II and III gliomas, the sensitivity was 80% (95% CI: 52-96%) and specificity was 100% (95% CI: 40-100%). Among 2-HG ratios, the highest AUC for the identification of IDH mutant status was achieved using the 2-HG/NAA (AUC = 0.8, 95% CI 0.67-.89). DATA CONCLUSION: Preoperative edited MRS appears to be able to help identify IDH-mutant gliomas with high specificity. Level of Evidence 1 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53:416-426.

Prospective comparative diagnostic accuracy evaluation of dynamic contrast-enhanced (DCE) vs. dynamic susceptibility contrast (DSC) MR perfusion in differentiating tumor recurrence from radiation necrosis in treated high-grade gliomas.

BACKGROUND: The appearance of a new enhancing lesion after surgery and chemoradiation for high-grade glioma (HGG) presents a common diagnostic dilemma. Histopathological analysis remains the reference standard in this situation. PURPOSE: To prospectively compare the diagnostic accuracy of dynamic contrast-enhanced (DCE) vs. dynamic susceptibility contrast (DSC) in differentiating tumor recurrence (TR) from radiation necrosis (RN). STUDY TYPE: Prospective diagnostic accuracy study. POPULATION: In all, 98 consecutive treated HGG patients with new enhancing lesion. We excluded 32 patients due to inadequate follow-up or technical limitation. FIELD STRENGTH/SEQUENCE: 3 T DCE and DSC MR. ASSESSMENT: Histogram and hot-spot analysis of cerebral blood volume (CBV), corrected CBV, Ktrans , area under the curve (AUC), and plasma volume (Vp). The reference standard of TR and/or RN was determined by histopathology in 43 surgically resected lesions or by clinical/imaging follow-up in the rest. STATISTICAL TESTS: Mann-Whitney U-tests, receiver operating characteristic (ROC) curve, and logistic regression analysis. RESULTS: A total of 68 lesions were included. There were 37 TR, 28 RN, and three lesions with equal proportions of TR and RN. TR had significantly higher CBV, corrected CBV, CBV ratio, corrected CBV ratio, AUC ratio, and Vp ratio (P < 0.05) than RN on hot-spot analysis. CBV had the highest diagnostic accuracy (AUROC 0.71). On histogram analysis, TR had higher CBV and corrected CBV maximal value compared with RN (P = 0.006, AUROC = 0.70). Only CBV on hot-spot analysis remained significant after correction for multiple comparison, with no significant improvement in diagnostic accuracy when using a combination of parameters (AUROC 0.71 vs. 0.76, P = 0.24). DATA CONCLUSION: DSC-derived CBV is the most accurate perfusion parameter in differentiating TR and RN. DSC and DCE-derived parameters reflecting the blood volume in an enhancing lesion are more accurate than the DCE-derived parameter Ktrans . Clinical practice may be best guided by blood volume measurements, rather than permeability assessment for differentiation of TR from RN. LEVEL OF EVIDENCE: 1 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2019;50:573-582.

Principles of T2 *-weighted dynamic susceptibility contrast MRI technique in brain tumor imaging.

Dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) is used to track the first pass of an exogenous, paramagnetic, nondiffusible contrast agent through brain tissue, and has emerged as a powerful tool in the characterization of brain tumor hemodynamics. DSC-MRI parameters can be helpful in many aspects, including tumor grading, prediction of treatment response, likelihood of malignant transformation, discrimination between tumor recurrence and radiation necrosis, and differentiation between true early progression and pseudoprogression. This review aims to provide a conceptual overview of the underlying principles of DSC-MRI of the brain for clinical neuroradiologists, scientists, or students wishing to improve their understanding of the technical aspects, pitfalls, and controversies of DSC perfusion MRI of the brain. Future consensus on image acquisition parameters and postprocessing of DSC-MRI will most likely allow this technique to be evaluated and used in high-quality multicenter studies and ultimately help guide clinical care.

Evaluation of perfusion CT in grading and prognostication of high-grade gliomas at diagnosis: a pilot study.

OBJECTIVE: Differentiation of grade 3 astrocytoma from glioblastoma multiforme can be difficult with conventional structural imaging but is important for prognosis. The purpose of this study was to assess perfusion CT in differentiating high-grade gliomas (HGGs) and their role in prognosis in the care of patients with HGG. SUBJECTS AND METHODS: Twenty patients with previously untreated HGG underwent prospective evaluation with perfusion CT. Permeability surface area product (PS) and cerebral blood volume (CBV) were calculated by the deconvolution method and were compared between HGGs with Student two-sample t tests. Receiver operating characteristic curves were generated for PS, CBV, and the conjoint factor PS + CBV. Cox regression analysis was used to correlate these parameters with patient survival over a follow-up period. Hazard ratios were calculated, and Kaplan-Meier survival curves were drawn. RESULTS: There was a significant difference between grade 3 and grade 4 gliomas for PS (p = 0.022) and PS + CBV (p = 0.019) but not for CBV alone (p = 0.411). Receiver operating characteristic analyses showed that PS (area under the curve [AUC], 0.72) and CBV + PS (AUC, 0.73) can be used to differentiate grade 3 from grade 4 gliomas but that CBV alone cannot be so used (AUC, 0.54). There was a significant relation between patient outcome and age (p = 0.034) and CBV + PS (p = 0.048). Patients with HGG and a CBV + PS greater than 9 had a poor outcome (hazard ratio, 6.00). CONCLUSION: PS and CBV + PS can be used to differentiate grade 3 from grade 4 gliomas. The outcome of patients with HGG depends on age and CBV + PS.

Enhancing Triplet-Triplet Upconversion Efficiency and Operational Lifetime in Blue Organic Light-Emitting Diodes by Utilizing Thermally Activated Delayed Fluorescence Materials.

In the process of triplet-triplet upconversion (TTU), a bright excited singlet can be generated because of the collision of two dark excited triplets. In particular, the efficiency of TTU is crucial for achieving a high exciton production yield in blue fluorescence organic light-emitting diodes (OLEDs) beyond the theoretical limit. While the theoretical upper limit of TTU contribution yield is expected to be 60%, blue OLEDs with the maximum TTU contribution are still scarce. Herein, we present a proof of concept for realizing the maximum TTU contribution yield in blue OLEDs, achieved through the doping of thermally activated delayed fluorescence (TADF) molecules in the carrier recombination zone. The bipolar carrier transport ability of TADF materials enables direct carrier recombination on the molecules, resulting in the expansion of the recombination zone. Although the external electroluminescence quantum efficiency of OLEDs is slightly lower than that of conventional TTU-OLEDs due to the low photoluminescence quantum yield of the doped layer, the TTU efficiency approaches the upper limit. Furthermore, the operational device lifetime of OLEDs employing TADF molecules increased by five times compared to the conventional ones, highlighting the expansion of the recombination zone as a crucial factor for enhancing overall OLED performance in TTU-OLEDs.

Computed tomography assessment of anterior ethmoidal canal dehiscence: An interobserver agreement study and review of the literature.

PURPOSE: The anterior ethmoidal artery can be injured in functional endoscopic sinus surgery. The ability of computed tomography (CT) to identify dehiscence of the anterior ethmoidal canal (AEC) has not been widely evaluated. The aim of this study was to evaluate the interobserver agreement in the CT assessment of AEC dehiscence. METHODS: We conducted a retrospective review of consecutive CT scans of the paranasal sinuses (PNS) between January 1, 2012, and December 31, 2012. Two neuroradiologists separately assessed the presence of AEC dehiscence, the presence of PNS opacification, and the best CT plane to evaluate the AEC. Statistical analysis included descriptive analysis and interobserver agreement (kappa coefficient). RESULTS: The AEC was below the skull base in 199 (22.3%) cases. Dehiscence of the AEC was found in 13.2% for reader 1 and in 7.3% for reader 2. The interobserver agreement for identification of AEC dehiscence was only fair (κ = 0.246). The interobserver agreement for the AEC dehiscence in cases with opacification of ethmoidal air cells was substantial (κ = 0.754). CONCLUSION: The suboptimal interobserver agreement could potentially limit the usefulness of CT scans for routine assessment of AEC dehiscence. In patients with PNS opacification, CT scans could still add valuable information regarding AEC dehiscence.

Imaging the Unconscious "Found Down" Patient in the Emergency Department.

Unconsciousness may be due to severe brain damage or to potentially reversible causes. Noncontrast head computed tomography (CT) helps identify acute ischemic and hemorrhagic lesions as well as certain patterns of toxic encephalopathy. MR imaging plays an important role in the assessment of acutely encephalopathic patients who may show no significant abnormality on CT. This review describes some of the common and infrequent entities that can lead to unconsciousness, including epilepsy and vascular, traumatic, metabolic, and toxic disorders.

Uncommon Cranial Meningioma: Key Imaging Features on Conventional and Advanced Imaging.

Given the high incidence of intracranial meningiomas encountered in clinical practice, it is not uncommon to find rare subtypes of meningioma, with unusual imaging findings. These commonly represent a diagnostic challenge. In this article, we review the imaging appearance of typical meningioma on conventional and advanced imaging as well as the key imaging features of multiple uncommon subtypes: cystic, microcystic, lipomatous, chordoid, angiomatous, intraosseous, extracranial, atypical/malignant, and tumor-to-tumor metastasis (also known as collision tumors). Some of these uncommon subtypes, however, demonstrate imaging features that may allow for a more specific diagnosis, or features, which can influence patient's management.

Acute anterior circulation stroke: recanalization using clot angioplasty.

BACKGROUND AND PURPOSE: Different strategies have been employed to recanalize acutely occluded middle cerebral and internal carotid arteries (ICA) in the setting of acute stroke including intravenous and intra-arterial tPA. However, pharmaceutical thrombolysis alone, may not be effective in patients with a large amount of clot volume (complete M1, terminal internal carotid artery). We report our initial experience with endovascular clot disruption using a soft silicone balloon in addition to intravenous or intra-arterial thrombolysis with tPA. METHODS: This is a retrospective review of nine patients with symptoms of acute stroke from clot in the middle cerebral or internal carotid territories who were treated with intracranial balloon angioplasty. All patients presented with symptoms of acute anterior circulation stroke less than six hours from onset. Patients in whom computed tomography (CT) angiography confirmed the presence of large vessel clot (terminal ICA, M1 or proximal M2) were included in the study. A CT perfusion was performed providing maps of cerebral blood volume, flow and mean transit time. If the patient presented less than three hours from onset then intravenous tissue plasminogen activator (tPA) was also administered. Intra-arterial tPA was delivered into the clot. If the volume of clot was judged to be significant by the treating neurointerventionist, then a limited trial of tPA was administered intra-arterially followed by balloon angioplasty of persistant clot. The time from imaging to vessel recanalization was recorded. Clinical outcomes were assessed using the modified Rankin scale and Barthel Index. RESULTS: Diagnostic CT perfusion studies were performed in 7 (78%), all of which showed a significant amount of salvageable tissue as judged by the treating neurointerventionist and neurologist. Recanalization (TIMI 2 or 3) was possible in 8 (89%). There were no cases of symptomatic intracranial hemorrhage and 2 (22%) asymptomatic hemorrhages. The average time from performance of the initial emergency CT to vessel recanalization was 2.1 hours with mean time from symptom onset to vessel recanalization of 4.1 hours. Five (56%) patients had good outcomes, 1 (11%) had mild and 3 (33%) had moderate to severe disability. CONCLUSION: Clot angioplasty can potentially shorten recanalization times in well-selected patients and can be an effective complimentary procedure in patients with tPA resistant clot. Angioplasty can be performed with a very low complication rate using the technique described and may be associated with good outcomes.

Radiological and pathological features associated with IDH1-R132H mutation status and early mortality in newly diagnosed anaplastic astrocytic tumours.

BACKGROUND: Glioblastoma can occur either de novo or by the transformation of a low grade tumour; the majority of which harbor a mutation in isocitrate dehydrogenase (IDH1). Anaplastic tumours are high-grade gliomas that may represent the final step in the evolution of a secondary glioblastoma or the initial presentation of an early primary glioblastoma. We sought to determine whether pathological and/or radiological variables exist that can reliably distinguish IDH1-R132H-positive from IDH1-R132H-negative tumours and to identify variables associated with early mortality. METHODS: Patients diagnosed with anaplastic astrocytic tumours were included. Magnetic resonance imaging was performed and immunohistochemistry was used to identify tumours with the IDH1-R132H mutation. Survival was assessed 12 months after diagnosis. Variables associated with IDH1-R132H status were identified by univariate and ROC analysis. RESULTS: 37 gliomas were studied; 18 were positive for the IDH1-R132H mutation. No tumours demonstrated a combined loss of chromosomes 1p/19q. Patients with IDH1-R132H-positive tumours were less likely to die within 12 months of diagnosis (17% vs. 47%; p=0.046), more likely to have tumours located in the frontal lobe (55% vs. 16%; p=0.015), and have a higher minimum apparent diffusion coefficient (1.115 x 10-3 mm2/sec vs. 0.838 x 10-3 mm2/sec; p=0.016), however, these variables demonstrated only moderate strength for predicting the IDH1-R132H mutation status (AUC=0.735 and 0.711, respectively). The Ki-67 index was significantly lower in IDH1-R132H-positive tumours (0.13 vs. 0.21; p=0.034). An increased risk of death was associated with contrast-enhancement ≥ 5 cm3 in patients with IDH1-R132H-positive tumours while edema ≥ 1 cm beyond the tumour margin and < 5 mitoses/mm2 were associated with an increased risk of death in patients with IDH1-R132H-negative tumours. CONCLUSIONS: IDH1-R132H-positive and -negative anaplastic tumours demonstrate unique features. Factors associated with early mortality are also dependent on IDH1-R132H status and can be used to identify patients at high risk for death.