Edzard Wiener

In vivo viscoelastic properties of the brain in normal pressure hydrocephalus

Nearly half a century after the first report of normal pressure hydrocephalus (NPH), the pathophysiological cause of the disease still remains unclear. Several theories about the cause and development of NPH emphasize disease‐related alterations of the mechanical properties of the brain. MR elastography (MRE) uniquely allows the measurement of viscoelastic constants of the living brain without intervention. In this study, 20 patients (mean age, 69.1 years; nine men, 11 women) with idiopathic (n = 15) and secondary (n = 5) NPH were examined by cerebral multifrequency MRE and compared with 25 healthy volunteers (mean age, 62.1 years; 10 men, 15 women). Viscoelastic constants related to the stiffness (µ) and micromechanical connectivity (α) of brain tissue were derived from the dynamics of storage and loss moduli within the experimentally achieved frequency range of 25–62.5 Hz. In patients with NPH, both storage and loss moduli decreased, corresponding to a softening of brain tissue of about 20% compared with healthy volunteers (p < 0.001). This loss of rigidity was accompanied by a decreasing α parameter (9%, p < 0.001), indicating an alteration in the microstructural connectivity of brain tissue during NPH. This disease‐related decrease in viscoelastic constants was even more pronounced in the periventricular region of the brain. The results demonstrate distinct tissue degradation associated with NPH. Further studies are required to investigate the source of mechanical tissue damage as a potential cause of NPH‐related ventricular expansions and clinical symptoms. Copyright

4-D Imaging in Cerebrovascular Disorders by Using 320-Slice CT: Feasibility and Preliminary Clinical Experience

RATIONALE AND OBJECTIVES The authors report study protocols and initial clinical experience in assessing patients with acute and chronic cerebrovascular disorders using the recently introduced technique of volume computed tomography (VCT). MATERIALS AND METHODS Thirteen patients with presumptive cerebrovascular insufficiency underwent VCT using a 320-slice scanner (detector width, 160 mm), including time-resolved whole-brain perfusion and cerebral angiography (four-dimensional computed tomographic angiography [CTA] and computed tomographic perfusion [CTP]). Unenhanced cranial CT (cCT) and helical cervicocranial CT (three-dimensional CTA) were added according to clinical requirements. Study protocols are presented, and image quality, data management, and radiation exposure issues are discussed. RESULTS In 12 of 13 patients, the procedure was performed successfully on admission; in the other patient, the study was aborted for clinical reasons and repeated. Total scan time amounted to about 5 minutes, and data reconstruction times were up to 10 minutes. About 9000 primary images were generated, partially in the enhanced Digital Imaging and Communications in Medicine format, thus requiring new data postprocessing and management strategies. Image artifacts restricted the use of single-rotation cCT and incremental VCT (three-dimensional CTA). Overall exposure figures (computed tomographic dose index and dose-length product) were increased by 65% on average when three-dimensional CTA was added to volume cCT and four-dimensional CTA and CTP (5.0 mSv and 2178 mGy . cm, respectively). CONCLUSION Preliminary clinical experience indicates that whole-brain four-dimensional CTA and CTP is a robust technique that provides relevant clinical information with respect to whole-brain perfusion as well as cerebral hemodynamics. The exposure benefit of deriving time-resolved perfusion and vessel images from one source data set is compromised when adding three-dimensional CTA to the protocol. Other acquisition techniques specific to VCT, such as single-rotation cCT and incremental three-dimensional CTA, suffer from restrictions in terms of image quality at present.

Computer-assisted detection of pulmonary nodules: performance evaluation of an expert knowledge-based detection system in consensus reading with experienced and inexperienced chest radiologists

To evaluate the performance of experienced versus inexperienced radiologists in comparison and in consensus with an interactive computer-aided detection (CAD) system for detection of pulmonary nodules. Eighteen consecutive patients (mean age: 62.2 years; range 29–83 years) prospectively underwent routine 16-row multislice computed tomography (MSCT). Four blinded radiologists (experienced: readers 1, 2; inexperienced: readers 3, 4) assessed image data against CAD for pulmonary nodules. Thereafter, consensus readings of readers 1+3, reader 1+CAD and reader 3+CAD were performed. Data were compared against an independent gold standard. Statistical tests used to calculate interobserver agreement, reader performance and nodule size were Kappa, ROC and Mann–Whitney U. CAD and experienced readers outperformed inexperienced readers (Az=0.72, 0.71, 0.73, 0.49 and 0.50 for CAD, readers 1–4, respectively; P<0.05). Performance of reader 1+CAD was superior to single reader and reader 1+3 performances (Az=0.93, 0.72 for reader 1+CAD and reader 1+3 consensus, respectively, P<0.05). Reader 3+CAD did not perform superiorly to experienced readers or CAD (Az=0.79 for reader 3+CAD; P>0.05). Consensus of reader 1+CAD significantly outperformed all other readings, demonstrating a benefit in using CAD as an inexperienced reader replacement. It is questionable whether inexperienced readers can be regarded as adequate for interpretation of pulmonary nodules in consensus with CAD, replacing an experienced radiologist.

Morphometric and volumetric MRI changes in idiopathic intracranial hypertension

Objective We aimed at validating established imaging features of idiopathic intracranial hypertension (IIH) by using state-of-the-art MR imaging together with advanced post-processing techniques and correlated imaging findings to clinical scores. Methods Twenty-five IIH patients as well as age-, sex- and body mass index (BMI)-matched controls underwent high-resolution T1w and T2w MR imaging in a 1.5 T scanner, followed by assessment of optic nerve sheaths, pituitary gland, ventricles and Meckels cave. Imaging findings were correlated with cerebrospinal fluid (CSF) opening pressures and clinical symptom scores of visual disturbances (visual field defects or enlarged blind spot), headache, tinnitus (pulsatile and non-pulsatile) and vertigo. CSF as well as ventricle volumes were determined by using an automated MRI volumetry algorithm. Results So-called ‘empty sella’ and optic nerve sheath distension were identified as reliable imaging signs in IIH. Posterior globe flattening turned out as a highly specific but not very sensitive sign. No abnormalities of the lateral ventricles were observed. These morphometric results could be confirmed using MR volumetry (VBM). Clinical symptoms did not correlate with an increase in lumbar opening pressure. Conclusions Our study results indicate that lateral ventricle size is not affected in IIH. In contrast, abnormalities of the pituitary gland and optic nerve sheath were reliable diagnostic signs for IIH.

A new case of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids

Sir, We read with great interest the recent article published in Brain by Pittock and colleagues (2010) describing eight patients with a previously unrecognized distinct brainstem encephalitis named chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Here, we report on what we believe to be another patient with CLIPPERS, lending further support to the concept that CLIPPERS is a novel, definable, inflammatory CNS disease. The patient provided written informed consent for presentation of her case as a report. A 69-year-old female noticed general weakness, dizziness and abnormal fatigue with subacute onset 16 weeks prior to evaluation at the Department of Neurology, Charite, Universitatsmedizin, Berlin. Eleven weeks prior, the patient developed horizontal diplopia and walking difficulties that gradually worsened so that she became unable to walk without assistance. Additionally, she noticed dysarthria and dysphagia as well as facial tingling and paraesthesia in her fingertips. About 4 weeks prior to admission, she developed hyperacusis and a labile affect with involuntary crying. Her past medical history was unremarkable except for arterial hypertension, which was treated with bisoprolol. Her family history was negative. Neurological examination on admission revealed a cerebellar syndrome with limb, gait and stance ataxia, as well as intention tremor on the left, more than on the right-hand side. She had marked cerebellar dysarthria. Her gait …

Outcome Prediction in Patients After Cardiac Arrest: A Simplified Method for Determination of Gray–White Matter Ratio in Cranial Computed Tomography

PurposeOut-of-hospital cardiac arrest is a frequent cause of death in Europe. Hypoxic ischemic encephalopathy (HIE) often develops in initial survivors, and the question of treatment limitation arises in severely affected patients. To establish a poor prognosis with a high level of certainty, the use of a combination of prognostic parameters such as neurological examination, somatosensory evoked potentials, and neuron-specific enolase is common practice. A few recent studies suggest that gray–white matter ratio (GWR) determined from cranial computed tomography (CT) scans is an additional reliable predictor of poor prognosis. The standard GWR determination method involves measurements of 16 different regions of interest (ROIs). We tested whether a simplified method to obtain GWR has equivalent reliability for poor outcome prediction.Materials and MethodsWe retrospectively analyzed 98 patients after cardiac arrest who had been treated with hypothermia. CT scans were obtained within the first 7 days after cardiac arrest. Neurological outcome was determined at intensive care unit discharge. Four different methods to obtain GWR were compared in a receiver-operating characteristic curve analysis with respect to their prognostic value for poor outcome prediction.ResultsThe simplest method using only four ROIs (putamen and internal capsule bilaterally) had the same prognostic value compared with the standard method using 16 ROIs. The simplified GWR predicted poor outcome with a sensitivity of 44 % at 100 % specificity.ConclusionOur results indicate that for poor outcome prediction in survivors of cardiac arrest, a simplified GWR determination is feasible and has the same reliability as the complex standard procedure.

Structural Olfactory Nerve Changes in Patients Suffering from Idiopathic Intracranial Hypertension

Background Complications of idiopathic intracranial hypertension (IIH) are usually caused by elevated intracranial pressure (ICP). In a similar way as in the optic nerve, elevated ICP could also compromise the olfactory nerve system. On the other side, there is growing evidence that an extensive lymphatic network system around the olfactory nerves could be disturbed in cerebrospinal fluid disorders like IIH. The hypothesis that patients with IIH suffer from hyposmia has been suggested in the past. However, this has not been proven in clinical studies yet. This pilot study investigates whether structural changes of the olfactory nerve system can be detected in patients with IIH. Methodology/Principal Findings Twenty-three patients with IIH and 23 matched controls were included. Olfactory bulb volume (OBV) and sulcus olfactorius (OS) depth were calculated by magnetic resonance techniques. While mean values of total OBV (128.7±38.4 vs. 130.0±32.6 mm3, p=0.90) and mean OS depth (8.5±1.2 vs. 8.6±1.1 mm, p=0.91) were similar in both groups, Pearson correlation showed that patients with a shorter medical history IIH revealed a smaller OBV (r=0.53, p<0.01). In untreated symptomatic patients (n=7), the effect was greater (r=0.76, p<0.05). Patients who suffered from IIH for less than one year (n=8), total OBV was significantly smaller than in matched controls (116.6±24.3 vs. 149.3±22.2 mm3, p=0.01). IIH patients with visual disturbances (n=21) revealed a lower OS depth than patients without (8.3±0.9 vs. 10.8±1.0 mm, p<0.01). Conclusions/Significance The results suggest that morphological changes of the olfactory nerve system could be present in IIH patients at an early stage of disease.

Quantitative imaging of the tissue contrast agent [Gd(DTPA)]2− in articular cartilage by laser ablation inductively coupled plasma mass spectrometry

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is an emerging analytical technique in the generation of quantitative images of MR contrast agent distribution in thin tissue sections of articular cartilage. An analytical protocol is described that includes sample preparation by cryo-cutting of tissue sections, mass spectrometric measurements by LA-ICP-MS and quantification of gadolinium images by one-point calibration, standard addition method (employing matrix-matched laboratory standards) and isotope dilution analysis using highly enriched stable Gd-155 isotope (abundance 92 vs 14.8% in the [Gd(DTPA)]²⁻ contrast agent). The tissue contrast agent concentrations of [Gd(DTPA)]²⁻ in cartilage measured in this work are in agreement with findings obtained by magnetic resonance imaging and other analytical methodologies. The LA-ICP-MS imaging data also confirm the observation that the spatial distribution of [Gd(DTPA)]²⁻ in the near-equilibrium state is highly inhomogeneous across cartilage thickness with the highest concentration measured in superficial cartilage and a strong decrease toward the subchondral bone. In the present work, it is shown for the first time that LA-ICP-MS can be applied to validate the results from quantitative gadolinium-enhanced MRI technique of articular cartilage.

Volumetric Assessment of Optic Nerve Sheath and Hypophysis in Idiopathic Intracranial Hypertension

BACKGROUND AND PURPOSE: Idiopathic intracranial hypertension is a headache syndrome characterized by increased CSF pressure. Compression of the hypophysis and distension of the optic nerve sheath are reliable imaging signs. The purpose of the study was to validate, in patients with idiopathic intracranial hypertension, MR imaging–based volumetric measurements of the optic nerve sheath and hypophysis as an objective observation method for more accurate diagnosis and posttreatment follow-up. MATERIALS AND METHODS: Twenty-three patients with idiopathic intracranial hypertension as well as age-, sex-, and body mass index–matched controls underwent volumetric measurements of the optic nerve, optic nerve sheath, and hypophysis on high-resolution T2-weighted MR images by using a 7-cm surface coil, followed by correlation with CSF opening pressures and clinical symptom scores of visual disturbances and headache. RESULTS: Mean values of optic nerve sheath (341.86 ± 163.69 mm3 versus 127.56 ± 53.17 mm3, P < .001) and hypophysis volumes (554.59 ± 142.82 mm3 versus 686.60 ± 137.84 mm3, P < .05) differed significantly between healthy and diseased subjects. No significant differences between mean optic nerve volumes were observed. Receiver operating characteristic analysis showed optic nerve sheath volumes of >201.30 mm3 (sensitivity, 86.96%; specificity, 91.30%) and hypophysis volumes of <611.21 mm3 (sensitivity, 78.26%; specificity, 69.57%) to be indicative of idiopathic intracranial hypertension diagnosis. In patients with idiopathic intracranial hypertension, no correlations were found between optic nerve sheath and hypophysis volumes and CSF opening pressures or clinical scores of visual disturbances and headache. CONCLUSIONS: Semiautomated volumetric measurement of optic nerve sheath and hypophysis has the potential to more accurately diagnose and follow patients with idiopathic intracranial hypertension.

Results for local control and functional outcome after linac-based image-guided stereotactic radiosurgery in 190 patients with vestibular schwannoma

Background We assessed local control (LC) and functional outcome after linac-based stereotactic radiosurgery (SRS) for vestibular schwannoma (VS). Methods Between 1998 and 2008, 190 patients with VS were treated with SRS. All patients had tumors <2 cm diameter. Patients received 13.5 Gy prescribed to the 80th isodose at the tumor margin. The primary endpoint was LC. Secondary endpoints were symptomatic control and morbidity. Results Median follow-up was 40 months. LC was achieved in 88% of patients. There were no acute reactions exceeding Grade I. Trigeminal nerve dysfunction was present in 21.6% (n = 41) prior to SRS. After treatment, 85% (n = 155) had no change, 4.4,% (n = 8) had a relief of symptoms, 10.4% (n = 19) had new symptoms. Facial nerve dysfunction was present in some patients prior to treatment, e.g. paresis (12.6%; n = 24) and dysgeusia (0.5%; n = 1). After treatment 1.1% (n = 2) reported improvement and 6.1% (n = 11) experienced new symptoms. Hearing problems before SRS were present in 69.5% of patients (n = 132). After treatment, 62.6% (n = 144) had no change, 10.4% (n = 19) experienced improvement and 26.9% (n = 49) became hearing impaired. Conclusion This series of SRS for small VS provided similar LC rates to microsurgery; thus, it is effective as a non-invasive, image-guided procedure. The functional outcomes observed indicate the safety and effectiveness of linac-based SRS. Patients may now be informed of the clinical equivalence of SRS to microsurgery.