Evaluation of novel 3D-printed and conventional thermoplastic stereotactic high-precision patient fixation masks for radiotherapy.

PURPOSE: For stereotactic radiation therapy of intracranial malignancies, a patient's head needs to be immobilized with high accuracy. Fixation devices such as invasive stereotactic head frames or non-invasive thermoplastic mask systems are often used. However, especially stereotactic high-precision masks often cause discomfort for patients due to a long manufacturing time during which the patient is required to lie still and because the face is covered, including the mouth, nose, eyes, and ears. To avoid these issues, the target was to develop a non-invasive 3D-printable mask system with at least the accuracy of the high-precision masks, for producing masks which can be manufactured in the absence of patients and which allow the eyes, mouth, and nose to be uncovered during therapy. METHODS: For four volunteers, a personalized 3D-printed mask based on magnetic resonance imaging (MRI) data was designed and manufactured using fused filament fabrication (FFF). Additionally, for each of the volunteers, a conventional thermoplastic stereotactic high-precision mask from Brainlab AG (Munich, Germany) was fabricated. The intra-fractional fixation accuracy for each mask and volunteer was evaluated using the motion-correction algorithm of functional MRI measurements with and without guided motion. RESULTS: The average values for the translations and rotations of the volunteers' heads lie in the range between ±1 mm and ±1° for both masks. Interestingly, the standard deviations and the relative and absolute 3D displacements are lower for the 3D-printed masks compared to the Brainlab masks. CONCLUSION: It could be shown that the intra-fractional fixation accuracy of the 3D-printed masks was higher than for the conventional stereotactic high-precision masks.

Neurobiological processes during the Cambridge gambling task.

Although vast research has been conducted concerning gambling behavior this is the first study combining behavioral and functional magnetic resonance imaging (fMRI) data while using the Cambridge Gambling Task (CGT). We tested 20 healthy right-handed men and chose an event-related design to allow for precise temporal separation of gambling stages. In the color decision stage participants had to guess whether a yellow token was hidden behind red or blue boxes presented in varying color ratios, then stake wagers during the bet decision stage. In the final stage the outcome (won or lost) was presented. Analyzing the blood-oxygenation level-dependent (BOLD) contrasts in the decision stages we found increases of activation in brain areas involved in decision making, working memory and learning, when participants bet on the majority choice. During the outcome stage increased brain activation was found in parts of the reward system and areas involved in decision making and impulse control, when winning. When losing, activation increased in areas involved in risk aversion and management of uncertainties. When participants lost unexpectedly (i.e. lost although they bet on the majority), increased activation was found in the insula, compared to winning expectedly. The more unexpectedly participants won the higher the increase of brain activation in parts of the reward system and areas involved in executive functions. Our study gives an extensive overview of brain areas involved in different stages of gambling and during various outcomes, with corresponding behavioral data (e.g. speed and quality of decision making) illustrating underlying tendencies.

An fMRI study of training voluntary smooth circular eye movements.

Despite a large number of recent studies, the promise of fMRI methods to produce valuable insights into motor skill learning has been restricted to sequence learning paradigms, or manual training paradigms where a relatively advanced capacity for sensory-motor integration and effector coordination already exists. We therefore obtained fMRIs from 16 healthy adults trained in a new paradigm that demanded voluntary smooth circular eye movements without a moving target. This aimed to monitor neural activation during two possible motor learning processes: (a) the smooth pursuit control system develops a new perceptual-motor relationship and successfully becomes involved in voluntary action in which it is not normally involved or (b) the saccadic system normally used for voluntary eye movement and which only exhibits linear action skill develops new dynamic coordinative control capable of smooth circular movement. Participants were able to improve within half an hour, typically demonstrating saccadic movement with progressively reduced amplitudes, which better approximated smooth circular movement. Activity in the inferior premotor cortex was significantly modulated and decreased during the progress of learning. In contrast, activations in dorsal premotor and parietal cortex along the intraparietal sulcus, the supplementary eye field and the anterior cerebellum did not change during training. Thus, the decrease of activity in inferior premotor cortex was critically related to the learning progress in visuospatial eye movement control.

Interactive knowledge discovery with the doctor-in-the-loop: a practical example of cerebral aneurysms research.

Established process models for knowledge discovery find the domain-expert in a customer-like and supervising role. In the field of biomedical research, it is necessary to move the domain-experts into the center of this process with far-reaching consequences for both their research output and the process itself. In this paper, we revise the established process models for knowledge discovery and propose a new process model for domain-expert-driven interactive knowledge discovery. Furthermore, we present a research infrastructure which is adapted to this new process model and demonstrate how the domain-expert can be deeply integrated even into the highly complex data-mining process and data-exploration tasks. We evaluated this approach in the medical domain for the case of cerebral aneurysms research.

MRI assessment of relapsed glioblastoma during treatment with bevacizumab: volumetric measurement of enhanced and FLAIR lesions for evaluation of response and progression--a pilot study.

PURPOSE: To develop a magnetic resonance imaging (MRI) metric that is useful for therapy monitoring in patients with relapsed glioblastoma (GBM) during treatment with the antiangiogenic monoclonal antibody bevacizumab (Bev). We evaluated the feasibility of tumour volume measurement with our software tool in clinical routine and tried to establish reproducible and quantitative parameters for surveillance of patients on treatment with antiangiogenic drugs. MATERIALS AND METHODS: In this retrospective institutional pilot study, 18 patients (11 men, 7 women; mean age 53.5) with recurrent GBM received bevacizumab and irinotecan every two weeks as second line therapy. Follow up scans were assessed every two to four months. Data were collected on a 1.5 T MR System (Siemens, Symphony) with the standard head coil using our standardized tumour protocol. Volumetric measurement was performed with a commercial available software stroketool in FLAIR and T1-c imaging with following procedure: Pre-processing involved cutting noise and electing a Gaussian of 3 × 3 to smooth images, selecting a ROI (region of interest) in healthy brain area of the contra lateral side with quantifying the intensity value, adding 20% to this value to define the threshold level. Only values above this threshold are left corresponding to the tumour lesion. For the volumetric measurement the detected tumour area was circuited in all slices and finally summing up all values and multiplied by slice thickness to get the whole volume. RESULTS: With McDonalds criteria progression was indicated in 14 out of 18 patients. In contrast, volumetric measurement showed an increase of contrast enhancement of >25%, defined as threshold for progression, in 11 patients (78%) and in 12 patients (85%) in FLAIR volume, respectively. 6 patients revealed that volumes in MRI increased earlier than the last scan, which was primarily defined as the date of progression with McDonald criteria, changing PFS after re-evaluation of the tumour volumes from 6.8 to 5.6 months. CONCLUSION: In this pilot study the applied imaging estimates objectively tumour response and progression compared to the bi-dimensional measurement. The quantitative parameters are reproducible and also applicable for the diffuse infiltrating lesions.

Involvement of area MT in bimanual finger movements in left-handers: an fMRI study.

The ease with which humans are able to perform symmetric movements of both hands has traditionally been attributed to the preference of the motor system to activate homologous muscles. Recently, we have shown in right-handers, however, that bimanual index finger adduction and abduction movements in incongruous hand orientations (one palm down/other up) preferentially engaged parietal perception-associated brain areas. Here, we used functional magnetic resonance imaging to investigate the influence of hand orientation in left-handers on cerebral activation during bimanual index finger movements. Performance in incongruous orientation of either hand yielded activations involving right and left motor cortex, supplementary motor area in right superior frontal gyrus (SMA and pre-SMA), bilateral premotor cortex, prefrontal cortex, bilateral somatosensory cortex and anterior parietal cortex along the intraparietal sulcus. In addition, the occipito-temporal cortex corresponding to human area MT (hMT) in either hemisphere was activated in relation to bimanual index finger movements in the incongruous hand orientation as compared with the same movements in the congruous hand orientation or with simply viewing the pacing stimuli. Comparison with the same movement condition in right-handed subjects from a former study support these hMT activations exclusively for left-handed subjects. These results suggest that left-handers use visual motion imagery in guiding incongruous bimanual finger movements.

Cerebrovascular biomodeling for aneurysm surgery: simulation-based training by means of rapid prototyping technologies.

OBJECTIVE: Opportunities for developing procedural skills are progressively rare. Therefore, sophisticated educational tools are highly warranted. METHODS: This study compared stereolithography and 3-dimensional printing for simulating cerebral aneurysm surgery. The latter jets multiple materials simultaneously and thus has the ability to print assemblies of multiple materials with different features. The authors created the solid skull and the cerebral vessels in different materials to simulate the real aneurysm when clipped. RESULTS: Precise plastic replicas of complex anatomical data provide intuitive tactile views that can be scrutinized from any perspective. Hollowed out vessel sections allow serial clipping efforts, evaluation of different clips, and clip positions. The models can be used for accurate prediction of vascular anatomy, for optimization of teaching surgical skills, for advanced procedural competency training, and for patient counseling. CONCLUSION: Simultaneous 3-dimensional printing is the most promising rapid prototyping technique to produce biomodels that meet the high demands of neurovascular surgery.

Assessment of gadolinium leakage into traumatic spinal cord lesion using magnet resonance imaging.

STUDY DESIGN: Exploratory study in patients with acute spinal cord trauma using magnetic resonance imaging (MRI). OBJECTIVE: The aim of this study was to assess the leakage of Gd-DTPA into traumatic lesions of the human spinal cord using MRI. SUMMARY OF BACKGROUND DATA: While MRI of acute spinal cord trauma is a routine type of clinical investigation, the time course of Gd-DTPA enhancement in traumatic spinal cord injury is not known. METHODS: In early stage after spinal cord injury (<24 hours) and at follow-up on day 4, 7, 14, 21, 28, and 84, the accumulation of Gd-DTPA within 30 minutes after bolus injection was investigated in sagittal and axial T2-weighted images and T1-weighted images. RESULTS: In 4 men aged between 23 and 55 years with severe paraparesis, the traumatic spinal cord lesion had a maximum of spatial extent after 7 days. Gd-enhancement was first detected on day 4 in T1-weighted images, was most pronounced between day 7 and 28 but absent on day 84. The Gd-enhancement progressively increased in intensity after intravenous injection between 5 and 10 minutes when a maximum was reached, which remained stable for up to 30 minutes. CONCLUSION: We used MRI to study the dynamics of post-traumatic Gd-DTPA leakage into the injured spinal cord. This appears as a promising approach for monitoring the local secondary lesion changes.

Effect of repetitive arm cycling following botulinum toxin injection for poststroke spasticity: evidence from FMRI.

BACKGROUND AND OBJECTIVE: Investigations were performed to establish if repetitive arm cycling training enhances the antispastic effect of intramuscular botulinum toxin (BTX) injections in postischemic spastic hemiparesis. Effects on cerebral activation were evaluated by functional magnetic resonance imaging (fMRI). METHODS: Eight chronic spastic hemisyndrome patients (49 ± 10 years) after middle cerebral artery infarction (5.5 ± 2.7 years) were investigated. BTX was injected into the affected arm twice, 6 months apart. Spasticity was assessed using the Ashworth Scale and range of motion before and 3 months after BTX injections. Images were analyzed using Brain Voyager QX 1.8, and fMRI signal changes were corrected for multiple comparisons. RESULTS: During passive movements of affected and nonaffected hands, fMRI activity was increased bilaterally in the sensorimotor cortex (MISI), secondary somatosensory areas (SII), and supplementary motor area predominantly in the contralesional hemisphere, compared with the rest. Following repetitive arm cycling, fMRI activity increased further in MISI of the lesioned hemisphere and SII of the contralesional hemisphere. For patients with residual motor activity, treatment-related fMRI activity increases were associated with reduced spasticity; in completely plegic patients, there was no fMRI activity change in SII but increased spasticity after training. CONCLUSION: Increased activity in SII of the contralesional hemisphere and in MISI of the lesioned hemisphere reflect a treatment-induced effect in the paretic arm. It is hypothesized that the increased BOLD activity results from increased afferent information related to the antispastic BTX effect reinforced by training.

Data-driven analyses of an fMRI study of a subject experiencing phosphenes.

PURPOSE: To compare two data-driven methods of statistical image analysis, principal and independent component analysis (PCA, ICA), in identifying neural networks related to the transient occurrence of phosphenes experienced by a female patient subsequent to a brain infarct. MATERIALS AND METHODS: An initial functional magnetic resonance imaging (fMRI) session consisted of two acquisitions: one of the patient experiencing phosphenes and a second responding to a well-defined visual stimulation paradigm. A second fMRI session 6 months later, when the patient no longer experienced phosphenes, consisted of an acquisition in which no stimulation was presented. Analysis of correlations between the temporal expression coefficients and models of the hemodynamic response identified salient components. Spectral analysis confirmed the identification. The phosphene model was based solely on the subjective report of the patient. RESULTS: Both methods revealed occipital cortical and subcortical areas known to be sites for visual information-processing during stimulation, as did SPM. In addition, higher-order visual areas such as the precuneus and the lateral parietal cortex were implicated in the PCA of the phosphenes. CONCLUSION: The analyses suggest the capability of data-driven approaches to identify the brain structures involved in these transient, spontaneous visual events.

Impact of fMRI-guided advanced DTI fiber tracking techniques on their clinical applications in patients with brain tumors.

INTRODUCTION: White matter tractography based on diffusion tensor imaging has become a well-accepted non-invasive tool for exploring the white matter architecture of the human brain in vivo. There exist two main key obstacles for reconstructing white matter fibers: firstly, the implementation and application of a suitable tracking algorithm, which is capable of reconstructing anatomically complex fascicular pathways correctly, as, e.g., areas of fiber crossing or branching; secondly, the definition of an appropriate tracking seed area for starting the reconstruction process. Large intersubject, anatomical variations make it difficult to define tracking seed areas based on reliable anatomical landmarks. An accurate definition of seed regions for the reconstruction of a specific neuronal pathway becomes even more challenging in patients suffering from space occupying pathological processes as, e.g., tumors due to the displacement of the tissue and the distortion of anatomical landmarks around the lesion. METHODS: To resolve the first problem, an advanced tracking algorithm, called advanced fast marching, was applied in this study. The second challenge was overcome by combining functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) in order to perform fMRI-guided accurate definition of appropriate seed areas for the DTI fiber tracking. In addition, the performance of the tasks was controlled by a MR-compatible power device. RESULTS: Application of this combined approach to eight healthy volunteers and exemplary to three tumor patients showed that it is feasible to accurately reconstruct relevant fiber tracts belonging to a specific functional system. CONCLUSION: fMRI-guided advanced DTI fiber tracking has the potential to provide accurate anatomical and functional information for a more informed therapeutic decision making.

I know where you'll look: an fMRI study of oculomotor intention and a change of motor plan.

BACKGROUND: Electrophysiological studies in monkeys showed that the intention to perform a saccade and the covert change in motor plan are reflected in the neural activity of the posterior parietal cortex (PPC). METHODS: To investigate whether such covert intentional processes are demonstrable in humans as well we used event related functional MRI. Subjects were instructed to fixate a central target, which changed its color in order to indicate the direction of a subsequent saccade. Unexpectedly for the subjects, the color changed again in half of the trials to instruct a spatially opposite saccade. RESULTS: The double-cue induced synergistic and prolonged signals in early visual areas, the motion specific visual area V5, PPC, and the supplementary and frontal eye field. At the single subject level it became evident that the PPC split up in two separate subareas. In the posterior region, the signal change correlated with the change in motor plan: activation strongly decreased when the cue instructed an ipsiversive saccade while it strongly increased when it instructed a contraversive saccade. In the anterior region, the signal change was motor related irrespective of the spatial direction of the upcoming saccade. CONCLUSION: Thus, the human PPC holds at least two different areas for planning and executing saccadic eye movements.

Perceptual influence on bimanual coordination: an fMRI study.

In bimanual coordination subjects typically show a spontaneous preference for movement symmetry. While there is experimental evidence for the principle of muscle homology, recent evidence suggested that bimanual coordination may be mediated as perceptual goals (Mechsner et al., 2001). To explore this controversy we performed a fMRI study in 11 healthy, right-handed subjects using bimanual index finger abductions and adductions in a congruous condition, i.e. both palms down, and incongruous conditions with either the left or right palm up. Our fMRI data showed a widespread bihemispheric network mediating proprioceptive coordination of the two hands with significant differences mainly for a perceptual dissociation: in the incongruous conditions with the one palm up there was a BOLD signal increase in a bilateral frontoparietal network involving the motor and premotor cortical areas, particularly in the right palm-up condition. These results accord with the notion that perceptual cues play an important role in the control of bilateral hand movements.

Cortical and subcortical correlates of functional electrical stimulation of wrist extensor and flexor muscles revealed by fMRI.

The main scope of this study was to test the feasibility and reliability of FES in a MR-environment. Functional Electrical Stimulation (FES) is used in the rehabilitation therapy of patients after stroke or spinal cord injury to improve their motor abilities. Its principle lies in applying repeated electrical stimulation to the relevant nerves or muscles for eliciting either isometric or concentric contractions of the treated muscles. In this study we report cerebral activation patterns in healthy subjects undergoing fMRI during FES stimulation. We stimulated the wrist extensor and flexor muscles in an alternating pattern while BOLD-fMRI was recorded. We used both block and event-related designs to demonstrate their feasibility for recording FES activation in the same cortical and subcortical areas. Six out of fifteen subjects repeated the experiment three times within the same session to control intraindividual variance. In both block and event-related design, the analysis revealed an activation pattern comprising the contralateral primary motor cortex, primary somatosensory cortex and premotor cortex; the ipsilateral cerebellum; bilateral secondary somatosensory cortex, the supplementary motor area and anterior cingulate cortex. Within the same subjects we observed a consistent replication of the activation pattern shown in overlapping regions centered on the peak of activation. Similar time course within these regions were demonstrated in the event-related design. Thus, both techniques demonstrate reliable activation of the sensorimotor network and eventually can be used for assessing plastic changes associated with FES rehabilitation treatment.

Brain activity for peripheral biological motion in the posterior superior temporal gyrus and the fusiform gyrus: Dependence on visual hemifield and view orientation.

Biological motion, the movement of the human body presented by a small number of point lights, activates among other regions lining the posterior superior temporal sulcus (pSTS) and gyrus (pSTG) and of the fusiform gyrus. In previous studies with foveal stimuli the activity in the pSTS/pSTG was often confined to the right hemisphere and bilateral in fusiform gyrus. We presented biological motion stimuli in peripheral vision and measured the BOLD responses with functional MRI to test whether the right dominance in pSTS/pSTG also occurred with peripheral stimuli. We found activation exclusively in the right pSTG for both visual hemifields. In the fusiform gyrus activation was found in both hemispheres and for peripheral stimuli strongest for contralateral stimulation. However, in both fusiform gyri leftward-facing stimuli activated different subfields than rightward-facing stimuli, indicating a clustering of the selectivity for the orientation of the human body form. No such clustering was observed in the pSTG. The results indicate for the fusiform gyrus an organization with respect to the view orientation of the stimulus.

Brain activation in response to bladder filling and simultaneous stimulation of the dorsal clitoral nerve--an fMRI study in healthy women.

AIMS: Using functional magnetic resonance imaging (fMRI) we investigated the cortical and subcortical representations during bladder filling and the effect of simultaneous stimulation of the dorsal clitoral nerve on these cortical and subcortical structures. METHODS: After approval of the local ethics committee, 8 healthy females were included. Prior to scanning, subjects were catheterized and the bladder was filled until first desire to void occurred. In a block design protocol we performed repetitive manual bladder filling (FILLING) and emptying of additional 80 ml saline, alternating with rest conditions (REST) of constant bladder volume. The protocol was repeated with simultaneous stimulation of the dorsal clitoral nerve during the filling periods (COMBINED). Activation maps were calculated by means for 3 different contrasts: 1) FILLING>REST, 2) COMBINED>REST and 3) FILLING>COMBINED. RESULTS: A group analysis of contrast 1) showed activation of the right prefrontal and orbitofrontal cortices, the insula bilaterally, the left precuneus, the parietal operculum bilaterally, the cerebellum bilaterally (q(FDR)< or =0.001), the right anterior cingulate gyrus (q(FDR)< or =0.005) and the right anterior mid pons (q(FDR)< or =0.05). Contrast 2) showed activation in the right frontal area, the left insula, the parietal operculum bilaterally and the left cerebellum (q(FDR)< or =0.001). Deactivations were found in the middle frontal gyrus bilaterally and the post- and paracentral gyri bilaterally. Contrast 3) revealed stronger activation during FILLING in the bilateral frontal and prefrontal areas, the right anterior cingulated gyrus, and the right putamen (q(FDR)< or =0.05). Only the right insula showed stronger activation during the COMBINED condition. CONCLUSION: Simultaneous dorsal clitoral nerve stimulation during bladder filling reduced the activation of certain cortical areas suggesting a neuromodulatory effect of this stimulation on supraspinal centres involved in lower urinary tract control.

Interaction of visual hemifield and body view in biological motion perception.

The brain network for the recognition of biological motion includes visual areas and structures of the mirror-neuron system. The latter respond during action execution as well as during action recognition. As motor and somatosensory areas predominantly represent the contralateral side of the body and visual areas predominantly process stimuli from the contralateral hemifield, we were interested in interactions between visual hemifield and action recognition. In the present study, human participants detected the facing direction of profile views of biological motion stimuli presented in the visual periphery. They recognized a right-facing body view of human motion better in the right visual hemifield than in the left; and a left-facing body view better in the left visual hemifield than in the right. In a subsequent fMRI experiment, performed with a similar task, two cortical areas in the left and right hemispheres were significantly correlated with the behavioural facing effect: primary somatosensory cortex (BA 2) and inferior frontal gyrus (BA 44). These areas were activated specifically when point-light stimuli presented in the contralateral visual hemifield displayed the side view of their contralateral body side. Our results indicate that the hemispheric specialization of one's own body map extends to the visual representation of the bodies of others.

Handedness and functional MRI-activation patterns in sentence processing.

We investigate differences of cerebral activation in 12 right-handed and left-handed participants, respectively, using a sentence-processing task. Functional MRI shows activation of left-frontal and inferior-parietal speech areas (BA 44, BA9, BA 40) in both groups, but a stronger bilateral activation in left-handers. Direct group comparison reveals a stronger activation in right-frontal cortex (BA 47, BA 6) and left cerebellum in left-handers. Laterality indices for the inferior-frontal cortex are less asymmetric in left-handers and are not related to the degree of handedness. Thus, our results show that sentence-processing induced enhanced activation involving a bilateral network in left-handed participants.

Post-lesional cerebral reorganisation: evidence from functional neuroimaging and transcranial magnetic stimulation.

Reorganisation of cerebral representations has been hypothesised to underlie the recovery from ischaemic brain infarction. The mechanisms can be investigated non-invasively in the human brain using functional neuroimaging and transcranial magnetic stimulation (TMS). Functional neuroimaging showed that reorganisation is a dynamic process beginning after stroke manifestation. In the acute stage, the mismatch between a large perfusion deficit and a smaller area with impaired water diffusion signifies the brain tissue that potentially enables recovery subsequent to early reperfusion as in thrombolysis. Single-pulse TMS showed that the integrity of the cortico-spinal tract system was critical for motor recovery within the first four weeks, irrespective of a concomitant affection of the somatosensory system. Follow-up studies over several months revealed that ischaemia results in atrophy of brain tissue adjacent to and of brain areas remote from the infarct lesion. In patients with hemiparetic stroke activation of premotor cortical areas in both cerebral hemispheres was found to underlie recovery of finger movements with the affected hand. Paired-pulse TMS showed regression of perilesional inhibition as well as intracortical disinhibition of the motor cortex contralateral to the infarction as mechanisms related to recovery. Training strategies can employ post-lesional brain plasticity resulting in enhanced perilesional activations and modulation of large-scale bihemispheric circuits.