Longitudinal MRI findings in patients with newly diagnosed glioblastoma after intraoperative radiotherapy.

BACKGROUND AND PURPOSE: Post-radiation treatment effects (pseudoprogression/radionecrosis) may bias MRI-based tumor response evaluation. To understand these changes specifically after high doses of radiotherapy, we analyzed MRIs of patients enrolled in the INTRAGO study (NCT02104882), a phase I/II dose-escalation trial of intraoperative radiotherapy (20-40 Gy) in glioblastoma. METHODS: INTRAGO patients were evaluated and compared to control patients who received standard therapy with focus on contrast enhancement patterns/volume, T2 lesion volume, and mean rCBV. RESULTS: Overall, 11/15 (73.3%) INTRAGO patients (median age 60 years) were included. Distant failure was observed in 7/11 (63.6%) patients, local tumor recurrence in one patient (9.1%). On the first follow-up MRI all but one patient demonstrated enhancement of varying patterns around the resection cavity which were: in 2/11 (18.2%) patients thin and linear, in 7/11 (63.6%) combined linear and nodular, and in 1/11 (9.1%) voluminous, indistinct, and mesh-like. In the course of treatment, most patients developed the latter two patterns (8/11 [72.7%]). INTRAGO patients demonstrated more often combined linear and nodular and/or voluminous, indistinct, mesh-like components (8/11 [72.7%]) in comparison to control patients (3/12 [25%], P = 0.02). INTRAGO patients demonstrated significantly increasing enhancing lesion (P = 0.001) and T2 lesion volumes (P < 0.001) in the longitudinal non-parametric analysis in comparison to the control group. rCBV showed no significant differences between both groups. CONCLUSIONS: High doses of radiotherapy to the tumor cavity result in more pronounced enhancement patterns/volumes and T2 lesion volumes. These results will be useful for the response evaluation of patients exposed to high doses of radiotherapy in future studies.

Gadolinium Leakage in Ocular Structures Is Common in Lacunar Infarction.

Background and Purpose- We investigated the frequency and pattern of blood-brain barrier, as well as blood-retina barrier, impairment in acute lacunar infarction as demonstrated by hyperintense acute reperfusion marker and gadolinium leakage in ocular structures (GLOS), respectively, on fluid-attenuated inversion recovery images. Methods- Acute lacunar infarction patients who underwent repeated magnetic resonance imaging after intravenous contrast agent administration were identified and the presence of GLOS in the anterior chamber and vitreous body and hyperintense acute reperfusion marker noted on fluid-attenuated inversion recovery. Results- Overall, 24 acute lacunar infarction patients (median age 64.5 years; interquartile range, 54-78 years) were included. On contrast-enhanced fluid-attenuated inversion recovery, GLOS was observed in 11 (45.8%) patients: in 4 (16.7%) in the anterior chamber only and in 7 (29.2%) in the anterior chamber and vitreous body. In all patients, GLOS was bilateral and symmetrical. In patients with GLOS in the anterior chamber only, the time between initial and follow-up magnetic resonance imaging was significantly shorter (7.5 [interquartile range, 4.25-11.5] hours) compared with patients with GLOS in the anterior chamber and vitreous body (28 [interquartile range, 10-43] hours; P=0.047). Hyperintense acute reperfusion marker could not be demonstrated in any of the patients. Conclusions- In acute lacunar infarction patients, unlike hyperintense acute reperfusion marker, GLOS is a frequent finding and shows a similar temporal evolution like in larger ischemic stroke.

Contrast-enhanced fat-suppressed FLAIR for the characterization of leptomeningeal inflammation in optic neuritis.

BACKGROUND: Leptomeningeal contrast enhancement on fluid-attenuated inversion recovery (FLAIR) images has been reported in patients with multiple sclerosis and interpreted as a biomarker of inflammation. In this study, we sought to evaluate this phenomenon in patients with optic neuritis (ON). METHODS: A total of 42 patients with suspected ON were included in this prospective study and underwent a dedicated study magnetic resonance imaging (MRI) protocol including native and contrast-enhanced fat-suppressed thin-section axial and coronal FLAIR images on an 1.5 T magnetic resonance (MR) system. RESULTS: After diagnostic workup, 34 patients with final diagnosis of ON were analyzed in detail. On contrast-enhanced fat-suppressed FLAIR images, 25 (73.5%) patients with ON demonstrated perioptic leptomeningeal enhancement, and in 3 (8.8%) patients, this was even the only pathological MRI finding. In comparison, patients with perioptic leptomeningeal enhancement on contrast-enhanced fat-suppressed FLAIR images had a higher prevalence of additional hyperintense brain lesions ( p = 0.022) as well as cerebrospinal fluid (CSF)-specific oligoclonal bands ( p = 0.013) than patients without. CONCLUSION: Perioptic leptomeningeal contrast enhancement on fat-suppressed FLAIR images is a novel marker in ON and possibly reflects a leptomeningeal inflammatory process preceding or accompanying ON. Thin-section contrast-enhanced fat-suppressed FLAIR images might be a useful addition in MRI protocols for patients with suspected ON.

Assessment of collateral blood flow in patients with distal branch occlusion of the middle cerebral artery.

PURPOSE: Aim of this study was to evaluate the collateral blood flow between more distal branches of the middle cerebral artery (MCA) in the case of peripheral MCA branch occlusion on dynamic 4D angiograms. We sought to individually predict the finally resulting infarction volume with regard to the extent of collateral blood flow. METHODS: Overall, 35 acute ischemic stroke patients with peripheral MCA branch occlusion were included. Volumes of the ischemic infarctions and perfusion deficits were measured on diffusion-weighted images DWI and time-to-peak TTP (> 4 s). Collateral flow on 4D MR angiograms were classified as previously specified. RESULTS: On DWI, the ischemic lesions had a mean volume of 3.4 ± 15.1 mL while the mean volume on TTP (> 4 s) was significantly larger 22.0 ± 18.1 mL (P < 0.001). On dynamic 4D angiograms we observed grade 1 in 8 (22.9%), grade 2 in 4 (11.4%), grade 3 in 10 (28.6%), and grade 4 in 13 (37.1%) patients. In comparison to patients with better collateralization (grade 3-4) patients with less sufficient collateralization (grade 0-2) demonstrated larger infarction volumes on initial (11.1 mL (IQR 2.9-35.5) vs. 2.1 mL (IQR 0.5-4.5), P = 0.03) and follow-up DWI (15.5 mL (IQR 12.6-23.3) vs. 1.9 mL (IQR 0.5-4.5), P = 0.03) with prominent infarction growth (7.4 mL (IQR 2.6-10.1) vs. 0.9 mL (IQR 0.2-2.6), P = 0.08). CONCLUSIONS: In the majority of cases with distal MCA branch occlusion a good collateral blood flow has been observed. Nevertheless, in approximately one quarter of patients an insufficient collateral blood flow has been detected that was associated with substantial infarction growth.

FLAIR Vascular Hyperintensities Indicate Slow Poststenotic Blood Flow in ICA Stenosis.

PURPOSE: Occlusion or significant stenosis of the internal carotid artery (ICA) in the cervical segment is commonly associated with a poststenotic decrease in the downstream blood flow and perfusion. Fluid attenuated inversion recovery (FLAIR) vascular hyperintensities (FVH) are a phenomenon that represents slow arterial blood flow. In this study, we investigated the frequency and extent of FVH in the distal ICA in patients with proximal ICA stenosis. METHODS: We analyzed the magnetic resonance imaging (MRI) findings in 51 patients with a total of 60 cervical ICA stenoses with special focus on the frequency and extent of FVH in the area of the petrous segment of the ICA on FLAIR images and correlated these with Doppler/duplex sonography results. RESULTS: In 46 (76.7%) patients with ICA stenosis, FVH could be detected in the petrous segment of the ICA: in 19 (41.3%) patients a thin hyperintense rim near the vessel wall (grade 1), in 24 (52.2%) patients a strong hyperintense rim near the vessel wall (grade 2), and in 3 (6.5%) patients a hyperintense filling of the entire lumen (grade 3) was observed. The extent of FVH in the ICA in the petrous segment showed a high negative correlation with the poststenotic flow velocity (Spearman correlation, R = -0.75, p < 0.001), and moderate correlation with the degree of ICA stenosis (Spearman correlation, R = 0.51, p< 0.001). CONCLUSION: An FVH in the petrous ICA is commonly seen among patients with steno-occlusive disease in proximal ICA and could therefore be useful to recognize a proximal ICA stenosis even on FLAIR images.

Gadolinium leakage in ocular structures in optic neuritis.

BACKGROUND: We investigated the frequency of blood-retina barrier impairment in optic neuritis (ON) using gadolinium leakage in ocular structures (GLOS), a novel imaging marker on contrast enhanced fluid attenuated inversion recovery images (FLAIR). METHODS: In 12 patients with acute ON who underwent repeated MRI the presence of GLOS was noted on contrast-enhanced FLAIR. RESULTS: Bilateral GLOS was observed in 4 (33.3%): in 3 symmetrical, and in 1 asymmetrical. In the latter GLOS was ipsilateral to the ON. CONCLUSIONS: GLOS may be observed frequently in ON. Asymmetrical GLOS may be caused by a more local effect of ON.

Susceptibility Vessel Sign on T2*-Weighted Gradient Echo Imaging in Lacunar Infarction.

BACKGROUND/AIM: In stroke due to large vessel occlusion, thrombotic material can be demonstrated by the susceptibility vessel sign (SVS), a hypointense signal on T2*-weighted gradient echo magnetic resonance (GRE) images. In the present study, we evaluated the value of GRE for the detection of perforating artery occlusion in hyperacute lacunar infarction (LI). MATERIALS AND METHODS: The presence of SVS on GRE in 58 patients with LI who underwent magnetic resonance imaging within 24 hours after symptom onset was analyzed. RESULTS: On diffusion-weighted images (DWI), LI was found in the basal ganglia in 17.2%, internal capsule in 25.9%, corona radiata in 19.0%, thalamus in 32.8%, and brainstem in 5.2%. On GRE a subtle circumscribed hypointense signal at the lower edge of the LI consistent with SVS was detected in 11/58 (19%) patients. Patients with SVS had larger ischemic lesions on DWI (p=0.045). CONCLUSION: SVS on GRE may be useful for detection of perforating artery occlusion in a subset of patients with hyperacute LI.

Anatomical distribution of cerebral microbleeds and intracerebral hemorrhage in vertebrobasilar dolichoectasia.

OBJECTIVES: Vertebrobasilar dolichoectasia (VBD) is a dilatative arteriopathy associated with intracerebral hemorrhage. In the present study, we sought to evaluate the frequency and anatomical distribution of cerebral microbleeds (cMBs) and intracerebral hemorrhage (ICH) in VBD. METHODS: From a MRI database 94 VBD patients were identified and analyzed with special emphasis on cMBs and ICH on T2*-weighted gradient echo images (GRE) in relation to the established diagnostic MRI criteria of VBD (diameter, height, and lateral position). cMBs/ICH location was categorized into anterior/posterior circulation. Clinical information like demographic details, clinical symptoms, and comorbidities were abstracted from the case records. An extensive modelling approach using generalized linear mixed-effects models was used. RESULTS: Overall, 79 (84.0%) patients (mean age 72.1±10.0 years, 74.7% male) with a standard stroke MRI protocol including T2*-weighted images were included in the analysis. cMBs were observed in 38/79 (48.1%) patients, ranging from 1 to 84 cMBs per patient. In the posterior circulation cMBs were observed more frequently (34/38 (89.5%)) in comparison to the anterior circulation (24/38 (63.2%)). cMBs were observed in the thalamus in 20/38 (52.6%), hippocampus in 1/38 (2.6%), occipital lobe in 18/38 (47.4%), pons in 6/38 (15.8%), medulla oblongata in 2/38 (5.2%), and cerebellum in 14/38 (36.8%) patients. ICH was observed in only 6/79 (7.6%) patients. There were significantly more cMBs in the posterior- (NCMBs-PC = 1.717, 95%CI: 1.336-2.208, p = 0.0315) than in the anterior circulation. Logistic regression model showed a significant positive effect of clinical symptoms such as ischemic, TIA and hemorrhagic stroke on the presence of cMBs (OR = 3.34, 95%CI [2.0-5.57], p = 0.0184; ndf = 78, AIC = 107.51). General linear model showed that clinical symptoms have a highly significant effect on the number of cMBs (N = 2.78, 95%CI [2.51-3.07], p<2*10-16; ndf = 78, AIC = 1218). CONCLUSION: cMBs and ICH may be observed in the anterior and posterior circulation in VBD but they occur more frequently in the posterior circulation. Most common anatomical locations of cMBs in VBD were the thalamus, occipital lobe and cerebellum. This posterior dominance of cMBs and ICH in VBD might reflect a specific underlying vascular pathology.

FLAIR vascular hyperintensities and 4D MR angiograms for the estimation of collateral blood flow in anterior cerebral artery ischemia.

PURPOSE: To assess FLAIR vascular hyperintensities (FVH) and dynamic (4D) angiograms derived from perfusion raw data as proposed magnetic resonance (MR) imaging markers of leptomeningeal collateral circulation in patients with ischemia in the territory of the anterior cerebral artery (ACA). METHODS: Forty patients from two tertiary care university hospitals were included. Infarct volumes and perfusion deficits were manually measured on DWI images and TTP maps, respectively. FVH and collateral flow on 4D MR angiograms were assessed and graded as previously specified. RESULTS: Forty-one hemispheres were affected. Mean DWI lesion volume was 8.2 (± 13.9; range 0-76.9) ml, mean TTP lesion volume was 24.5 (± 17.2, range 0-76.7) ml. FVH were observed in 26/41 (63.4%) hemispheres. Significant correlations were detected between FVH and TTP lesion volume (ρ = 0.4; P<0.01) absolute (ρ = 0.37; P<0.05) and relative mismatch volume (ρ = 0.35; P<0.05). The modified ASITN/SIR score correlated inversely with DWI lesion volume (ρ = -0.58; P<0.01) and positively with relative mismatch (ρ = 0.29; P< 0.05). ANOVA of the ASITN/SIR score revealed significant inter-group differences for DWI (P<0.001) and TTP lesion volumes (P<0.05). No correlation was observed between FVH scores and modified ASITH/SIR scores (ρ = -0.16; P = 0.32). CONCLUSIONS: FVH and flow patterns on 4D MR angiograms are markers of perfusion deficits and tissue at risk. As both methods did not show a correlation between each other, they seem to provide complimentary instead of redundant information. Previously shown evidence for the meaning of these specific MR signs in internal carotid and middle cerebral artery stroke seems to be transferrable to ischemic stroke in the ACA territory.

Hyperintense Acute Reperfusion Marker on FLAIR in Posterior Circulation Infarction.

PURPOSE: In the present study, we aimed to investigate the frequency of blood brain barrier injury in posterior circulation infarction as demonstrated by the hyperintense acute reperfusion marker (HARM) on fluid attenuated inversion recovery images (FLAIR). METHODS: From a MRI report database we identified patients with posterior circulation infarction who underwent MRI, including perfusion-weighted images (PWI), within 12 hours after onset and follow-up MRI within 24 hours and analyzed diffusion-weighted images (DWI), PWI, FLAIR, and MR angiography (MRA). On FLAIR images, the presence of HARM was noted by using pre-specified criteria (focal enhancement in the subarachnoid space and/or the ventricles). RESULTS: Overall 16 patients (median age of patients 68.5 (IQR 55.5-82.75) years) with posterior circulation infarction were included. Of these, 13 (81.3%) demonstrated PCA occlusion, and 3 (18.7%) patients BA occlusion on MRA. Initial DWI demonstrated ischemic lesions in the thalamus (68.8%), splenium (18.8%), hippocampus (75%), occipital lobe (81.3%), mesencephalon (18.8%), pons (18.8%), and cerebellum (50%). On follow-up MRA recanalization was noted in 10 (62.5%) patients. On follow-up FLAIR images, HARM was observed in 8 (50%) patients. In all of these, HARM was detected remote from the acute ischemic lesion. HARM was more frequently observed in patients with vessel recanalization (p = 0.04), minor infarction growth (p = 0.01), and smaller ischemic lesions on follow-up DWI (p = 0.05). CONCLUSIONS: HARM is a frequent finding in posterior circulation infarction and associated with vessel recanalization, minor infarction growth as well as smaller infarction volumes in the course. Neuroradiologists should be cognizant of the fact that HARM may be present on short interval follow-up FLAIR images in patients with acute ischemic infarction who initially underwent MRI and received intravenous gadolinium-based contrast agents.

Perfusion-weighted imaging and dynamic 4D angiograms for the estimation of collateral blood flow in lacunar infarction.

Although lacunar infarction accounts for approximately 25% of ischemic strokes, collateral blood flow through anastomoses is not well evaluated in lacunar infarction. In 111 lacunar infarction patients, we analyzed diffusion-weighted images, perfusion-weighted images, and blood flow on dynamic four-dimensional angiograms generated by use of Signal Processing In NMR-Software. Blood flow was classified as absent (type 1), from periphery to center (type 2), from center to periphery (type 3), and combination of type 2 and 3 (type 4). On diffusion-weighted images, lacunar infarction was found in the basal ganglia (11.7%), internal capsule (24.3%), corona radiata (30.6%), thalamus (24.3%), and brainstem (9.0%). In 58 (52.2%) patients, perfusion-weighted image showed a circumscribed hypoperfusion, in one (0.9%) a circumscribed hyperperfusion, whereas the remainder was normal. In 36 (62.1%) patients, a larger perfusion deficit (>7 mm) was observed. In these, blood flow was classified type 1 in four (11.1%), 2 in 17 (47.2%), 3 in 9 (25.0%), and 4 in six (16.7%) patients. Patients with lacunar infarction in the posterior circulation more often demonstrated blood flow type 2 and less often type 3 (p = 0.01). Detailed examination and graduation of blood flow in lacunar infarction by use of dynamic four-dimensional angiograms is feasible and may serve for a better characterization of this stroke subtype.

Value of dynamic susceptibility contrast perfusion MRI in the acute phase of transient global amnesia.

PURPOSE: Transient global amnesia (TGA) is a transitory, short-lasting neurological disorder characterized by a sudden onset of antero- and retrograde amnesia. Perfusion abnormalities in TGA have been evaluated mainly by use of positron emission tomography (PET) or single-photon emission computed tomography (SPECT). In the present study we explore the value of dynamic susceptibility contrast perfusion-weighted MRI (PWI) in TGA in the acute phase. METHODS: From a MRI report database we identified TGA patients who underwent MRI including PWI in the acute phase and compared these to control subjects. Quantitative perfusion maps (cerebral blood flow (CBF) and volume (CBV)) were generated and analyzed by use of Signal Processing In NMR-Software (SPIN). CBF and CBV values in subcortical brain regions were assessed by use of VOI created in FIRST, a model-based segmentation tool in the Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL). RESULTS: Five TGA patients were included (2 men, 3 women). On PWI, no relevant perfusion alterations were found by visual inspection in TGA patients. Group comparisons for possible differences between TGA patients and control subjects showed significant lower rCBF values bilaterally in the hippocampus, in the left thalamus and globus pallidus as well as bilaterally in the putamen and the left caudate nucleus. Correspondingly, significant lower rCBV values were observed bilaterally in the hippocampus and the putamen as well as in the left caudate nucleus. Group comparisons for possible side differences in rCBF and rCBV values in TGA patients revealed a significant lower rCBV value in the left caudate nucleus. CONCLUSIONS: Mere visual inspection of PWI is not sufficient for the assessment of perfusion changes in TGA in the acute phase. Group comparisons with healthy control subjects might be useful to detect subtle perfusion changes on PWI in TGA patients. However, this should be confirmed in larger data sets and serial PWI examinations.