MR features of intracranial hemangioblastomas.

The contribution of MR in 10 patients with surgically proven intracranial hemangioblastomas was retrospectively evaluated and correlated with the computed tomographic findings. Angiography was obtained in eight cases. Multiple lesions were shown in only two patients, but none proved to have von Hippel-Lindau disease. In six patients the tumor typically appeared as a cystic lesion with an intensely enhancing mural nodule at the pial surface of the cyst; three patients presented with a solid lesion with a central cyst and one with a solid lesion only. Thirteen tumors were located in the posterior fossa, with one in the brain stem extending towards the spinal cord. A supratentorial localization was found in two patients. Abnormal serpiginous vessels supplying or draining the mural nodule or solid lesion were not visualized on contrast-enhanced computed tomography, but were easily identified as flow voids on MR in five patients. Calcification or hemorrhage were not seen in the entire series. Because of the multiplanar imaging capability and the lack of streak artifacts from the petrous bone, MR provides better localization than CT. MR is more accurate in predicting the number, extension and vascularity of hemangioblastomas, and provides a sound basis for further diagnostic and therapeutic procedures.     

Deep processing activates the medial temporal lobe in young but not in old adults

Age-related impairments in episodic memory have been related to a deficiency in semantic processing, based on the finding that elderly adults typically benefit less than young adults from deep, semantic as opposed to shallow, nonsemantic processing of study items. In the present study, we tested the hypothesis that elderly adults are not able to perform certain cognitive operations under deep processing conditions. We further hypothesised that this inability does not involve regions commonly associated with lexical/semantic retrieval processes, but rather involves a dysfunction of the medial temporal lobe (MTL) memory system. To this end, we used functional MRI on rather extensive groups of young and elderly adults to compare brain activity patterns obtained during a deep (living/nonliving) and a shallow (uppercase/lowercase) classification task. Common activity in relation to semantic classification was observed in regions that have been previously related to semantic retrieval, including mainly left-lateralised activity in the inferior prefrontal, middle temporal, and middle frontal/anterior cingulate gyrus. Although the young adults showed more activity in some of these areas, the finding of mainly overlapping activation patterns during semantic classification supports the idea that lexical/semantic retrieval processes are still intact in elderly adults. This received further support by the finding that both groups showed similar behavioural performances as well on the deep and shallow classification tasks. Importantly, though, the young revealed significantly more activity than the elderly adults in the left anterior hippocampus during deep relative to shallow classification. This finding is in line with the idea that age-related impairments in episodic encoding are, at least partly, due to an under-recruitment of the medial temporal lobe memory system.     

Rapid acquisition of two-way active avoidance in inbred Roman Low Avoidance rats

Two inbred strains of rats, derived from the Roman High Avoidance and Roman Low Avoidance selection lines, were tested for performance on the two-way active avoidance task which had been used during selection. Both inbred strains rapidly acquired the avoidance response and showed nearly perfect avoidance from trial 40 through trial 50. Probably, genes responsible for the low avoidance performance in the RLA strain disappeared during inbreeding.     

Segmental IMRT for oropharyngeal cancer in a clinical setting.

BACKGROUND AND PURPOSE: To develop a segmental intensity-modulated radiotherapy (IMRT) technique for the treatment of oropharyngeal cancer. PATIENTS AND METHODS: Eight patients previously treated for oropharyngeal cancer were replanned with segmental IMRT. The dose distribution was optimized using beam geometries consisting of 3, 5, 7 and 9 equiangular beams. The optimization procedure resulted in a theoretical fluence for each beam. In order to vary the number of segments, the optimized fluence was divided into four different equidistant levels. The final dose distribution was calculated using clinically deliverable segments obtained from optimized fluence. RESULTS: For our segmental IMRT technique the dose homogeneity within the target volumes improved when the total number of segments increased and reached a saturation level at approximately 150 segments. Seven beams were sufficient to achieve the saturation level for dose homogeneity. The mean dose to the parotid glands depended on the beam geometry and tumor location and did not depend on the number of segments. On average the mean dose to the contralateral parotid gland was 35.7 Gy (27.1-39.9 Gy) for all seven beam plans. CONCLUSIONS: Seven beams are sufficient to achieve an acceptable dose homogeneity within the target volumes and significant parotid sparing. These results will be used to introduce IMRT in routine clinical practice.     

CaMKIIδ and cardiomyocyte Ca2+ signalling new perspectives on splice variant targeting

Control of cardiomyocyte cytosolic Ca²⁺ levels is crucial in determining inotropic status and ischemia/reperfusion stress response. Responsive to fluctuations in cellular Ca²⁺, Ca²⁺/calmodulin‐dependent protein kinase II (CaMKII) is a serine/threonine kinase integral to the processes regulating cardiomyocyte Ca²⁺ channels/transporters. CaMKII is primarily expressed either in the δ_B or δ_C splice variant forms, which may mediate differential influences on cardiomyocyte function and pathological response mechanisms. Increases in myocyte Ca²⁺ levels promote the binding of a Ca²⁺/calmodulin complex to CaMKII, to activate the kinase. Activity is also maintained through a series of post‐translational modifications within a critical region of the regulatory domain of the protein. Recent data indicate that the post‐translational modification status of CaMKIIδ_B/δ_C variants may have an important influence on reperfusion outcomes. This study provided the first evidence that the specific type of CaMKII post‐translational modification has a role in determining target selectivity of downstream Ca²⁺ transporters. The study was also able to demonstrate that the phosphorylated form of CaMKII closely co‐localizes with CaMKIIδ_B in the nuclear/myofilament fraction, contrasting with a co‐enrichment of oxidized CaMKII in the membrane fraction with CaMKIIδ_C. It has also been possible to conclude that a hyper‐phosphorylation of CaMKII (Thr287) in reperfused hearts represents a hyper‐activation of the CaMKIIδ_B, which exerts anti‐arrhythmic actions through an enhanced capacity to selectively increase sarcoplasmic reticulum Ca²⁺ uptake and maintain cytosolic Ca²⁺ levels. This suggests that suppression of global CaMKIIδ may not be an efficacious approach to developing optimal pharmacological interventions for the vulnerable heart.     

Experimental verification of magnetic field dose effects for the MRI-accelerator

The MRI-linear accelerator system, currently being developed, is designed such that the patient is irradiated in the presence of a magnetic field. This influences the dose distribution due to the Lorentz force working on the secondary electrons. Simulations have shown that the following dose effects occur: the build-up distance is reduced, the lateral profile becomes asymmetric in the direction orthogonal to the magnetic field and at tissue-air interfaces the dose increases due to returning electrons. In this work, GafChromic film measurements were performed in the presence of a magnetic field to experimentally quantify these dose effects. Depth-dose curves were measured in a PMMA-air-PMMA phantom and the lateral profiles were measured in a homogeneous PMMA phantom with the photon beam protruding over the edges of the phantom. The measurement results confirmed the magnetic field dose effects that were predicted by simulations. This enabled us to verify Geant4 Monte Carlo simulations of these MRI-linac specific dose effects: the relative agreement for the depth-dose curves between measurements and simulations was within 2.2%/1.8 mm. The relative agreement for the lateral profiles was 2.3%/1.7 mm. Overall, the magnetic field dose effects that are expected for irradiation with the MRI-linac can be modelled using Geant4 Monte Carlo simulations within measurement accuracy.