Elke Hattingen

Quantitative MR Imaging of Brain Tissue and Brain Pathologies

Measurement of basic quantitative magnetic resonance (MR) parameters (e.g., relaxation times T1, T2*, T2 or respective rates R (1/T)) corrected for radiofrequency (RF)xa0coil bias yields different conventional and new tissue contrasts as well as volumes for tissue segmentation. This approach also provides quantitative measures of microstructural and functional tissue changes. We herein demonstrate some prospects of quantitative MR imaging in neurological diagnostics and science.

Imaging Biomarkers for Adult Medulloblastomas: Genetic Entities May Be Identified by Their MR Imaging Radiophenotype

BACKGROUND AND PURPOSE: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas. MATERIALS AND METHODS: Eligible preoperative MRIs from 28 patients (11 women; 22–53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists. Lesions and perifocal edema were volumetrized and multiparametrically evaluated for classic morphologic characteristics, location, hydrocephalus, and Chang criteria. To identify MR imaging biomarkers, we correlated genetic entities sonic hedgehog (SHH) TP53 wild type, wingless (WNT), and non-WNT/non-SHH medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study. RESULTS: There were 19 SHH TP53 wild type (69%), 4 WNT-activated (14%), and 5 Group 4 (17%) medulloblastomas. Six potential MR imaging biomarkers were identified, 3 of which, hydrocephalus (P = .03), intraventricular macrometastases (P = .02), and hemorrhage (P = .04), when combined, could identify WNT medulloblastoma with 100% sensitivity and 88.3% specificity (95% CI, 39.8%–100.0% and 62.6%–95.3%). WNT-activated nuclear β-catenin accumulating medulloblastomas were smaller than the other entities (95% CI, 5.2–22.3 cm3 versus 35.1–47.6 cm3; P = .03). Hemorrhage was exclusively present in non-WNT/non-SHH medulloblastomas (P = .04; n = 2/5). MR imaging biomarkers were all discordant from those identified in the pediatric cohort. Desmoplastic/nodular medulloblastomas were more rarely in contact with the fourth ventricle (4/15 versus 7/13; P = .04). CONCLUSIONS: MR imaging biomarkers can help distinguish histologic and genetic medulloblastoma entities in adults and appear to be different from those identified in children.

White matter alterations of the corticospinal tract in adults born very preterm and/or with very low birth weight.

White matter (WM) injury, either visible on conventional magnetic resonance images (MRI) or measurable by diffusion tensor imaging (DTI), is frequent in preterm born individuals and often affects the corticospinal tract (CST). The relation between visible and invisible white mater alterations in the reconstructed CST of preterm subjects has so far been studied in infants, children and up to adolescence. Therefore, we probabilistically tracked the CST in 53 term‐born and 56 very preterm and/or low birth weight (VP/VLBW,u2009<u200932 weeks of gestation and/or birth weightu2009<u20091,500 g) adults (mean age 26 years) and compared their DTI parameters (axial, radial, mean diffusivity—AD, RD, MD, fractional anisotropy—FA) in the whole CST and slice‐wise along the CST. Additionally, we used the automatic, tract‐based‐spatial‐statistics (TBSS) as an alternative to tractography. We compared control and VP/VLBW and subgroups with and without CST WM lesions visible on conventional MRI. Compared to controls, VP/VLBW subjects had significantly higher diffusivity (AD, RD, MD) in the whole CST, slice‐wise along the CST, and in multiple regions along the TBSS skeleton. VP/VLBW subjects also had significantly lower (TBSS) and higher (tractography) FA in regions along the CST, but no different mean FA in the tracked CST as a whole. Diffusion changes were weaker, but remained significant for both, tractography and TBSS, when excluding subjects with visible CST lesions. Chronic CST injury persists in VP/VLBW adults even in the absence of visible WM lesions, indicating long‐term structural WM changes induced by premature birth. Hum Brain Mapp 37:289–299, 2016.

Quantitative T1‐mapping detects cloudy‐enhancing tumor compartments predicting outcome of patients with glioblastoma

Contrast enhancement of glioblastomas (GBM) is caused by the decrease in relaxation time, T1. Here, we demonstrate that the quantitative measurement of T1 (qT1) discovers a subtle enhancement in GBM patients that is invisible in standard MRI. We assessed the volume change of this “cloudy” enhancement during radio‐chemotherapy and its impact on patients’ progression‐free survival (PFS). We enrolled 18 GBM patients in this observational, prospective cohort study and measured 3T‐MRI pre‐ and post contrast agent with standard T1‐weighted (T1w) and with sequences to quantify T1 before radiation, and at 6‐week intervals during radio‐chemotherapy. We measured contrast enhancement by subtracting pre from post contrast contrast images, yielding relative signal increase ∆T1w and relative T1 shortening ∆qT1. On ∆qT1, we identified a solid and a cloudy‐enhancing compartment and evaluated the impact of their therapy‐related volume change upon PFS. In ∆qT1 maps cloudy‐enhancing compartments were found in all but two patients at baseline and in all patients during therapy. The qT1 decrease in the cloudy‐enhancing compartment post contrast was 21.64% versus 1.96% in the contralateral control tissue (P < 0.001). It was located at the margin of solid enhancement which was also seen on T1w. In contrast, the cloudy‐enhancing compartment was visually undetectable on ∆T1w. A volume decrease of more than 21.4% of the cloudy‐enhancing compartment at first follow‐up predicted longer PFS (P = 0.038). Cloudy‐enhancing compartment outside the solid contrast‐enhancing area of GBM is a new observation which is only visually detectable with qT1‐mapping and may represent tumor infiltration. Its early volume decrease predicts a longer PFS in GBM patients during standard radio‐chemotherapy.

Effects of arterial input function selection on kinetic parameters in brain dynamic contrast-enhanced MRI

PURPOSEnKinetic parameters derived from dynamic contrast-enhanced MRI (DCE-MRI) were suggested as a possible instrument for multi-parametric lesion characterization, but have not found their way into clinical practice yet due to inconsistent results. The quantification is heavily influenced by the definition of an appropriate arterial input functions (AIF). Regarding brain tumor DCE-MRI, there are currently several co-existing methods to determine the AIF frequently including different brain vessels as sources. This study quantitatively and qualitatively analyzes the impact of AIF source selection on kinetic parameters derived from commonly selected AIF source vessels compared to a population-based AIF model.nnnMATERIAL AND METHODSn74 patients with brain lesions underwent 3D DCE-MRI. Kinetic parameters [transfer constants of contrast agent efflux and reflux Ktrans and kep and, their ratio, ve, that is used to measure extravascular-extracellular volume fraction and plasma volume fraction vp] were determined using extended Tofts model in 821 ROI from 4 AIF sources [the internal carotid artery (ICA), the closest artery to the lesion, the superior sagittal sinus (SSS), the population-based Parker model]. The effect of AIF source alteration on kinetic parameters was evaluated by tissue type selective intra-class correlation (ICC) and capacity to differentiate gliomas by WHO grade [area under the curve analysis (AUC)].nnnRESULTSnArterial AIF more often led to implausible ve >100% values (p<0.0001). AIF source alteration rendered different absolute kinetic parameters (p<0.0001), except for kep. ICC between kinetic parameters of different AIF sources and tissues were variable (0.08-0.87) and only consistent >0.5 between arterial AIF derived kinetic parameters. Differentiation between WHO III and II glioma was exclusively possible with vp derived from an AIF in the SSS (p=0.03; AUC 0.74).nnnCONCLUSIONnThe AIF source has a significant impact on absolute kinetic parameters in DCE-MRI, which limits the comparability of kinetic parameters derived from different AIF sources. The effect is also tissue-dependent. The SSS appears to be the best choice for AIF source vessel selection in brain tumor DCE-MRI as it exclusively allowed for WHO grades II/III and III/IV glioma distinction (by vp) and showed the least number of implausible ve values.

Combining rheology and MRI: Imaging healthy and tumorous brains based on mechanical properties

It is well known that pathological changes in tissue alter its mechanical properties. This holds also true for brain tissue. In case of the brain, however, obtaining information about these properties is hard due to the surrounding cranial bone. In this paper a novel technique to create an imaging contrast based on the aforementioned properties is presented.

Brain relaxometry after macrocyclic Gd-based contrast agent

PurposeTo assess if ratios of T1-weighted (T1w) signal intensity (SI) and quantitative T1xa0relaxometry (qT1) change on serial administration of macrocyclic gadobutrol.MethodsA total of 17xa0glioblastoma patients were scanned at 3.0u2009T magnetic resonance imaging (MRI) every 6 weeks after tumor resection with standard MRI and T1 and T2 relaxometry before and after gadobutrol administration. On co-registered images T1w SI was measured and relaxation times T1 (qT1) and quantitative T2 (qT2) were quantified in several deep grey matter nuclei as ratios relative to frontal white matter and to the pons. Ratio changes were evaluated over time with axa0paired t‑test and multiple regression.ResultsAn average ofxa08 (rangexa05–14) scans per patient were completed. Ratios of T1w SI, qT1 and qT2 remained unchanged for all target regions from the first to the last time point (pxa0> 0.05) and did not correlate with the number of gadobutrol administrations. Multivariate regression showed no significant impact of gadobutrol on qT1 or qT2 ratios, but axa0significant negative effect on T1w SI ratios. Gender also had no impact on the ratios but age had axa0significant negative influence on the qT1xa0ratio.ConclusionMultiple administrations of axa0macrocyclic contrast agent did not change relaxation time T1xa0ratios in any deep grey matter structure.

Bildgebende Diagnostik von Gliomen

Die Bildgebung dient zur praoperativen Differenzialdiagnostik einer zerebralen Raumforderung, zur Operationsplanung und -kontrolle sowie zum Therapiemonitoring. Wichtigste Methode ist hierbei die Magnetresonanztomografie (MRT), die aufgrund ihres hohen Weichteilkontrasts und der 3D-Hirndarstellung anderen bildgebenden Verfahren bei den meisten Fragestellungen uberlegen ist. Dieses Kapitel gibt einen Einblick in wichtige Grundzuge, Moglichkeiten und Grenzen der Bildgebung in der Tumordiagnostik. In Zukunft wird das molekulare Profil der Tumore fur Diagnose, Prognose und Therapieentscheidung immer bedeutender; entsprechend wird sich die Rolle der Bildgebung andern. Vor diesem Hintergrund werden nur die wichtigsten Differenzialdiagnosen in der praoperativen Bildgebung sowie die Bedeutung verschiedener MR-Methoden fur Operationsplanung und Therapiemonitoring genannt.

Multicenter pilot study of radio-chemotherapy as first-line treatment for adults with medulloblastoma (NOA-07)

BackgroundnMedulloblastoma in adult patients is rare, with 0.6 cases per million. Prognosis depends on clinical factors and medulloblastoma entity. No prospective data on the feasibility of radiochemotherapy exist. The German Neuro-Oncology Working Group (NOA) performed a prospective descriptive multicenter single-arm phase II trial to evaluate feasibility and toxicity of radio-polychemotherapy.nnnMethodsnThe NOA-07 trial combined craniospinal irradiation with vincristine, followed by 8 cycles of cisplatin, lomustine, and vincristine. Adverse events, imaging and progression patterns, histological and genetic markers, health-related quality of life (HRQoL), and cognition were evaluated. Primary endpoint was the rate of toxicity-related treatment terminations after 4 chemotherapy cycles, and the toxicity profile. The feasibility goal was reached if at least 45% of patients received at least 4 cycles of maintenance chemotherapy.nnnResultsnThirty patients were evaluable. Each 50% showed classic and desmoplastic/nodular histology. Sixty-seven percent were classified into the sonic hedgehog (SHH) subgroup without TP53 alterations, 13% in wingless (WNT), and 17% in non-WNT/non-SHH. Four cycles of chemotherapy were feasible in the majority (n = 21; 70.0%). Hematological side effects and polyneuropathy were prevalent toxicities. During the active treatment period, HRQoL and verbal fluency improved significantly. The 3-year event-free survival rate was 66.6% at the time of databank lock.nnnConclusionsnRadio-polychemotherapy did lead to considerable toxicity and a high amount of dose reductions throughout the first 4 chemotherapy cycles that may affect efficacy. Thus, we propose frequent patient surveillance using this regimen. Modifications of the regimen may increase feasibility of radio-polychemotherapy of adult patients with medulloblastoma.

Limbic Encephalitis in Patients with Epilepsy—is Quantitative MRI Diagnostic?

PurposeLimbic encephalitis (LE) is an immune-related disease with limbic symptoms, variable and asymmetric magnetic resonance imaging (MRI) aspects and antibody profiles. This study investigated the diagnostic value of quantitative relaxation times T2 (qT2) and MRI signal intensities (SI) in LE.MethodsThe prospective 3T-MRI study included 39xa0epilepsy patients with initially suspected LE and 20xa0healthy controls. Values and asymmetry indices of qT2, T2-weighted (T2-w) and proton density (PD)-w SI of manually delineated and automatically segmented amygdala and hippocampus were measured. Additionally, two raters made axa0blinded visual analysis on FLAIR (fluid attenuation inversion recovery) and T2-w images.ResultsAccording to diagnostic guidelines, 22xa0patients had probable LE and 17xa0patients had possible LE. The qT2 was higher (pu202f<u20090.01) in patients than in controls (meanu202f±u2009SD, amygdala 98u202f±u20097u202fms vs. 90u202f±u20095u202fms, hippocampus 101u202f±u20097u202fms vs. 92u202f±u20093u202fms), but was not different between probable and possible LE or between sides (left and right). The PD-w SI and T2-w SI were lower in patients than in controls but were not different between patient subgroups or between sides. Diagnostic performance of visual analysis was relatively poor.ConclusionsEpilepsy patients with suspected LE had elevated qT2 in amygdala and hippocampus, whereas the expected T2-w SI increase was not found; however, the diagnostic value of qT2 remains questionable since it did not discriminate probable from possible LE.