Marco Essig

Stereotactic fractionated radiotherapy for chordomas and chondrosarcomas of the skull base

PURPOSE To investigate the treatment outcome of patients suffering from skull base chordoma or chondrosarcoma after fractionated stereotactic radiotherapy. METHODS AND MATERIALS We report 45 patients treated for chordoma or chondrosarcoma with postoperative fractionated stereotactic radiotherapy between 1990 and 1997. Patients had CT and MRI for 3D treatment planning performed under stereotactic guidance. Median dose at isocenter was 66.6 Gy for chordomas and 64.9 Gy for chondrosarcomas. MRI imaging was obtained in intervals after therapy to evaluate local relapse. Survival was calculated according to the Kaplan-Meier method. RESULTS All chondrosarcomas had achieved and maintained local control and recurrence-free status at follow-up of 5 years. Local control rate of chordomas was 82% at 2 years and 50% at 5 years. Survival was 97% at 2 years and 82% at 5 years. At maximum follow-up of 8 years local control and survival rate of chordomas was 40% (82%). Clinically significant late toxicity developed in one patient. CONCLUSIONS Our results demonstrate the feasibility of fractionated photon beam therapy and its success in the treatment of skull base tumors. Modern 3D treatment techniques provide superior results compared to conventional techniques. The role of high-precision radiotherapy compared to particle beam therapy in the treatment of these tumors is not yet fully clear and further research is needed.

Neutralization of CD95 ligand promotes regeneration and functional recovery after spinal cord injury

The clinical outcome of spinal cord injury (SCI) depends in part on the extent of secondary damage, to which apoptosis contributes. The CD95 and tumor necrosis factor (TNF) ligand/receptor systems play an essential role in various apoptotic mechanisms. To determine the involvement of these ligands in SCI-induced damage, we neutralized the activity of CD95 ligand (CD95L) and/or TNF in spinal cord-injured mice. Therapeutic neutralization of CD95L, but not of TNF, significantly decreased apoptotic cell death after SCI. Mice treated with CD95L-specific antibodies were capable of initiating active hind-limb movements several weeks after injury. The improvement in locomotor performance was mirrored by an increase in regenerating fibers and upregulation of growth-associated protein-43 (GAP-43). Thus, neutralization of CD95L promoted axonal regeneration and functional improvement in injured adult animals. This therapeutic strategy may constitute a potent future treatment for human spinal injury.

Diagnostic performance of spectroscopic and perfusion MRI for distinction of brain tumors

Objective: To assess the value of spectroscopic and perfusion MRI for glioma grading and for distinguishing glioblastomas from metastases and from CNS lymphomas. Methods: The authors examined 79 consecutive patients with first detection of a brain neoplasm on nonenhanced CT scans and no therapy prior to evaluation. Spectroscopic MRI; arterial spin-labeling MRI for measuring cerebral blood flow (CBF); first-pass dynamic, susceptibility-weighted, contrast-enhanced MRI for measuring cerebral blood volume; and T1-weighted dynamic contrast-enhanced MRI were performed. Receiver operating characteristic analysis was performed, and optimum thresholds for tumor classification and glioma grading were determined. Results: Perfusion MRI had a higher diagnostic performance than spectroscopic MRI. Because of a significantly higher tumor blood flow in glioblastomas compared with CNS lymphomas, a threshold value of 1.2 for CBF provided sensitivity of 97%, specificity of 80%, positive predictive value (PPV) of 94%, and negative predictive value (NPV) of 89%. Because CBF was significantly higher in peritumoral nonenhancing T2-hyperintense regions of glioblastomas compared with metastases, a threshold value of 0.5 for CBF provided sensitivity, specificity, PPV, and NPV of 100%, 71%, 94%, and 100%. Glioblastomas had the highest tumor blood flow values among all other glioma grades. For discrimination of glioblastomas from grade 3 gliomas, sensitivity was 97%, specificity was 50%, PPV was 84%, and NPV was 86% (CBF threshold value of 1.4), and for discrimination of glioblastomas from grade 2 gliomas, sensitivity was 94%, specificity was 78%, PPV was 94%, and NPV was 78% (CBF threshold value of 1.6). Conclusion: Perfusion MRI is predictive in distinguishing glioblastomas from metastases, CNS lymphomas and other gliomas vs MRI and magnetic resonance spectroscopy.

3D Radial Projection Technique With Ultrashort Echo Times for Sodium MRI: Clinical Applications in Human Brain and Skeletal Muscle

23Na MRI has the potential to noninvasively detect sodium (Na) content changes in vivo. The goal of this study was to implement 23Na MRI in a clinical setting for neurooncological and muscular imaging. Due to the biexponential T2 decay of the tissue Na signal with a short component, which ranges between 0.5–8 ms, the measurement of total Na content requires imaging techniques with echo times (TEs) below 0.5 ms. A 3D radial pulse sequence with a TE of 0.2 ms at a spatial resolution of 4 × 4 × 4 mm3 was developed that allows the acquisition and presentation of Na images on the scanner. This sequence was evaluated in patients with low‐ and high‐grade gliomas, and higher 23Na MR signals corresponding to an increased Na content were found in the tumor regions. The contrast‐to‐noise ratio (CNR) between tumor and white matter increased from 0.8 ± 0.2 to 1.3 ± 0.3 with tumor grade. In patients with an identified muscular 23Na channelopathy (Paramyotonia congenita (PC)), induced muscle weakness led to a signal increase of ∼18% in the 23Na MR images, which was attributed to intracellular Na+ accumulation in this region. Magn Reson Med 57:74–81, 2007.

Perfusion MRI: The Five Most Frequently Asked Technical Questions

OBJECTIVE This and its companion article address the 10 most frequently asked questions that radiologists face when planning, performing, processing, and interpreting different MR perfusion studies in CNS imaging. CONCLUSION Perfusion MRI is a promising tool in assessing stroke, brain tumors, and patients with neurodegenerative diseases. Most of the impediments that have limited the use of perfusion MRI can be overcome to allow integration of these methods into modern neuroimaging protocols.

Quantitative magnetic resonance imaging in geriatric depression and primary degenerative dementia

Quantitative magnetic resonance imaging (MRI) was used to investigate volumes of different brain structures in 19 patients with late-onset major depression (DSM-III-R), 27 patients with Alzheimers disease (NINCDS-ADRDA criteria) and 13 age matched controls. 3-D MRI sequences were acquired using a Siemens 1.5 T scanner. Whole brain volume, CSF volume, volume of the frontal and temporal lobes and the volume of the amygdala-hippocampus complex were assessed using the software NMR Win. Compared to the controls, depressed patients showed a significantly lower whole brain volume and a significantly higher CSF volume, whereas volumes of the frontal and temporal lobes as well as the amygdala-hippocampus complex volumes were not significantly decreased. In addition, depressed patients exhibited a higher ventricle-brain ratio suggesting a higher degree of central atrophy compared to healthy individuals. In contrast, Alzheimer patients showed significantly lower volumes than depressed patients and controls with respect to all volumetric parameters. Although the findings indicate the presence of brain atrophy in patients with late-onset depression, the pattern of volumetric changes in these patients differs markedly from that observed in patients with primary degenerative dementia.

Reduced cerebellar volume and neurological soft signs in first-episode schizophrenia

Recent studies indicate that morphological and functional abnormalities of the cerebellum are associated with schizophrenia. Since the cerebellum is crucial for motor coordination, one may ask whether the respective changes are associated with motor dysfunction in the disease. To test these hypotheses in a clinical study, we investigated cerebellar volumes derived from volumetric magnetic resonance imaging of 37 first-episode patients with schizophrenia, schizophreniform or schizoaffective disorder and 18 healthy controls matched for age, gender and handedness. To control for potential interindividual differences in head size, intracranial volume was entered as a covariate. Neurological soft signs (NSS) were examined after remission of acute symptoms. Compared with the controls, patients had significantly smaller cerebellar volumes for both hemispheres. Furthermore, NSS in patients were inversely correlated with tissue volume of the right cerebellar hemisphere partialling for intracranial volume. No associations were detected between cerebellar volumes and psychopathological measures obtained at hospital admission when patients were in the acute psychotic state or after remission, treatment duration until remission, treatment response or prognostic factors, respectively. These findings support the hypothesis of cerebellar involvement in schizophrenia and indicate that the respective changes are associated with NSS.

Influence of human serum albumin on longitudinal and transverse relaxation rates (r1 and r2) of magnetic resonance contrast agents.

Objectives:Exogenous magnetic resonance (MR) contrast media (CM) are used to improve detection and delineation of physiological and pathologic structures. Temporary binding between CM and proteins such as human serum albumin (HSA) may alter the relaxation-enhancing properties of specific contrast agents. In this study, the presence and strength of HSA interaction with different CM was investigated. Material and Methods:Three contrast agents were chosen: Gd-DTPA, Gd-BT-DO3A, and Gd-BOPTA, each of which is known to have a different protein interaction. Samples were prepared using 7 different HSA concentrations, all at a constant CM concentration of 0.5 mmol/L. The relaxation rates, R1 and R2, of each sample were measured at 1.5 T. Virtual docking studies were performed to estimate the number of high affinity-binding sites of Gd-BOPTA and the surface of the HSA dimer. Results:Gd-BOPTA caused the greatest increase in R1 and R2, which followed an exponential dependency with increasing HSA concentration. Between the range of 0 and 7 g/dL of HSA, Gd-DTPA and Gd-BT-DO3A showed a relative change in both relaxation rates of approximately 13% and 22% for R1 and 26% and 30% for R2, respectively. In contrast, Gd-BOPTA demonstrated a relative increase of approximately 108% and 363% for R1 and R2, respectively. Changes of HSA concentration within physiological range (3.5–5.5 g/dL) resulted in an increase of R1 and R2 of approximately 40% when using Gd-BOPTA. The docking study revealed that approximately 10 small hydrophobic pockets exist on the HSA surface where the aromatic tail of Gd-BOPTA can fit in and a stronger noncovalent binding can occur compared with Gd-DTPA and Gd-BT-DO3A. Conclusion:Relaxation rates of Gd-BOPTA showed a strong dependency on HSA. In contrast, Gd-DTPA and Gd-BT-DO3A demonstrated little or no relevant dependency. On the basis of these results, the influence of serum protein concentration should be considered in both research studies and in clinical use.

High-resolution MR venography of cerebral arteriovenous malformations

PURPOSE The purpose of this study was to evaluate the diagnostic potential of a high resolution MR venography technique in patients with cerebral arteriovenous malformations (AVM). A high-resolution 3D gradient echo sequence was used with a long echo time TE to obtain venous information down to sub-pixel sized vessel diameters of several hundred microns. The method is based on the paramagnetic property of deoxyhemoglobin and the resulting developing phase difference between veins and brain parenchyma at long echo times which leads to signal cancellation. The reconstructed venograms were compared with TOF-MR angiography using qualitative and quantitative criteria with the conventional DSA serving as the reference gold standard. METHODS In 17 patients with angiographically proven cerebral AVM the method indicates its potential in clinical applications. Venography was able to detect all AVM whereas TOF-MRA failed in three patients. In the delineation of venous drainage patterns MR venography was superior to TOF-MRA, however, as expected the method detected only about half of the main feeding arteries. Due to susceptibility artifacts at air/tissue boundaries or interference with paramagnetic hemosiderin, MR venography was limited with respect to the delineation of the exact nidus sizes and shapes in ten patients with AVM located close to the skull base or in patients having suffered from previous bleeding. RESULTS Although the visualization of draining veins represents an important prerequisite in the surgical and radiosurgical treatment planning of cerebral AVM, there exist limitations of the technique in regions where strong induced static field inhomogeneities are present. CONCLUSIONS Due to its high sensitivity the method may be of special importance in the early detection and assessment of small AVM which are difficult to diagnose with other MR methods.

High-resolution venography of the brain using magnetic resonance imaging

The purpose of this study was to evaluate a non-flow related magnetic resonance imaging method to visualize small veins independent of arteries in the human brain. A long TE, high-resolution 3D gradient echo MR acquisition was used to highlight venous information. The method is based on the paramagnetic property of deoxyhemoglobin and the resulting phase difference between veins and brain parenchyma at long echo times. The MR magnitude images were masked with a phase mask filter to enhance small structure visibility.. Venous information down to sub-pixel vessel diameters of several hundred microns is visible. Venous data are displayed in an angiographic manner using a minimum intensity projection algorithm. Both superficial veins and deep white matter veins are visible. The method has been successfully applied in volunteers. Preliminary results in patients with cerebral arteriovenous malformations indicate its potential in clinical applications. The proposed method is easy to implement and does not require administration of a contrast agent or application of specially designed rf pulses to highlight the veins. Rather it exploits the intrinsic magnetic properties (BOLD-effect) and the prolonged T2* of venous blood. The method may be of diagnostic potential in the assessment of arteriovenous malformations or other vascular venous lesions.