Direct visualization of cerebellar nuclei in patients with focal cerebellar lesions and its application for lesion-symptom mapping.

As yet, human cerebellar lesion studies have not taken advantage of direct magnetic resonance imaging (MRI) of the cerebellar nuclei in individual patients. In the present study, susceptibility weighted imaging (SWI) was used to visualize lesions of the dentate nuclei in patients with chronic focal lesions. Fifteen patients with cerebellar lesions either due to stroke or tumor surgery underwent SWI imaging using a 1.5T MRI scanner. Dentate nuclei were seen as hypointensities in all patients. Three of the patients underwent additional SWI imaging at 3T and 7T. Compared to 1.5T, corrugation of the dentate wall was seen with greater precision and the dorsal, iron-poorer part was seen more fully. Lesion-symptom mapping was performed based on the 1.5T MR images. Patients were divided into two groups with and without upper limb ataxia. A region-of-interest-(ROI)-driven normalization technique was used which had initially been developed by Diedrichsen et al. (2011) for functional MRI (fMRI) of the dentate nuclei. Compared to conventional normalization of the cerebellum, overlap of dentate lesions improved and lead to increased sensitivity of lesion-symptom maps. Subtraction analysis revealed that the more dorsal and rostral parts of the dentate nuclei were related to upper limb ataxia. Findings were in good accordance with the dentate hand area shown in recent fMRI studies. These data provide evidence that direct identification of dentate lesions together with the ROI-driven normalization technique allows for improved lesion-symptom mapping at the level of the cerebellar nuclei already at conventional 1.5T MRI field strength.

Impairments of prehension kinematics and grasping forces in patients with cerebellar degeneration and the relationship to cerebellar atrophy.

OBJECTIVE: This study established the relationship between kinematic and grip force parameters in prehension tasks, disease severity and cerebellar atrophy in patients with cerebellar degeneration. METHODS: Prehension was tested in a condition during which the hand reached out, grasped, and lifted an object. Task complexity was modified by limiting the transport component to a single-joint movement, and introducing a bimanual condition. RESULTS: Compared to controls the cerebellar patients showed disturbances in hand transport, in hand shaping and the most pronounced in time to peak grip force and the grip/load force coupling. Task-dependent changes did not differ between groups. Ataxia scores revealed significant correlations with hand transport and shaping measures only. Ataxia subscores correlated with volume reduction of appropriate longitudinal cerebellar zones. Volume reduction of the intermediate zone was associated with grip force coordination deficits. CONCLUSIONS: Results indicate that the cerebellum may have a more general role in motor control of grasping independent of task complexity. Temporal and coordinative measures of grip force appear to be most useful to assess the severity of grasping deficits in patients with cerebellar degeneration not detectable by clinical ataxia scales. SIGNIFICANCE: To assess the severity and course of cerebellar disease grip force control in a standard prehension task is a sensitive quantitative measure.

Trace eyeblink conditioning in patients with cerebellar degeneration: comparison of short and long trace intervals.

To elucidate whether the cerebellar cortex may contribute to trace eyeblink conditioning in humans, eight patients with degenerative cerebellar disorders (four with sporadic adult onset ataxia, three with autosomal dominant cerebellar ataxia type III and one with spinocerebellar ataxia type 6) and eight age- and sex-matched healthy control subjects were investigated. Individual high resolution three-dimensional MRI data sets were acquired. As revealed by volumetric measurements of the cerebellum using ECCET software, patients showed cerebellar atrophy to various degrees. No abnormalities were observed in the control subjects. Eyeblink conditioning was performed twice using a tone of 40 ms as conditioned stimulus, followed by a short (400 ms) and a long (1,000 ms) trace interval and an air-puff of 100 ms as unconditioned stimulus. Using the short trace interval, eyeblink conditioning was significantly impaired in cerebellar patients compared to controls, even in those who fulfilled criteria of awareness. Using the long trace interval no significant group differences could be observed. The present findings of impaired trace eyeblink acquisition in patients with cortical cerebellar degeneration suggest that the cerebellar cortex in humans, in addition to the interposed nucleus, is involved in trace eyeblink conditioning, if the trace interval is relatively short. Using a long trace interval, the cerebellum appears to be less important.

[Computerized analysis of brain perfusion parameter images]. / Automatisierte Analyse von Parameterbildern der Hirnperfusion.

PURPOSE: The development of a computerized method which allows a direct quantitative comparison of perfusion parameters. The display should allow a clear direct comparison of brain perfusion parameters in different vascular territories and over the course of time. The analysis is intended to be the basis for further evaluation of cerebral vasospasm after subarachnoid hemorrhage (SAH). The method should permit early diagnosis of cerebral vasospasm. MATERIALS AND METHODS: The Angiotux 2D-ECCET software was developed with a close cooperation between computer scientists and clinicians. Starting from parameter images of brain perfusion, the cortex was marked, segmented and assigned to definite vascular territories. The underlying values were averages for each segment and were displayed in a graph. If a follow-up was available, the mean values of the perfusion parameters were displayed in relation to time. The method was developed under consideration of CT perfusion values but is applicable for other methods of perfusion imaging. RESULTS: Computerized analysis of brain perfusion parameter images allows an immediate comparison of these parameters and follow-up of mean values in a clear and concise manner. Values are related to definite vascular territories. The tabular output facilitates further statistic evaluations. The computerized analysis is precisely reproducible, i. e., repetitions result in exactly the same output. CONCLUSION: Computerized analysis of brain perfusion parameters with Angiotux 2D-ECCET is objective and ensures reproducible results. It may become the basis and a requirement for the analysis of minimal changes in brain perfusion prior to irreversible damage from posthemorrhagic vasospasm.

Feasibility of ultra-low-dose multi-detector-row CT-colonography: detection of artificial endoluminal lesions in an in-vitro-model with optimization of image quality using a noise reduction filter algorithm.

PURPOSE: To assess the most favorable slice thickness in Multi-Detector-Row CT-colonography (MDCTC), and the feasibility of dose reduction in an in-vitro-setting as well as the possibility of optimization of image quality using a noise reduction filter algorithm. - MATERIALS AND METHODS: 18 artificial lesions with sizes from 1 to 8 mm were randomly positioned in two cleansed pig colons. At a "Somatom Plus 4 Volume Zoom", six scanning protocols using a slice collimation of 2.5, 1, and 1 mm with a reconstructed slice thickness of 3, 3, and 1.25 mm were performed with tube currents of 100, and 10 mAs, respectively. Using a non-commercial software, a non-linear Gaussian filter was used to minimize image noise. Image noise was assessed before and after application of the filtering process. Using a threshold of -750 HU, two blinded readers analyzed the virtual colonography in respect to lesion location, size, and shape. Artifacts were noted. An automated detection system was evaluated. - RESULTS: Using 10 mAs, a ten-fold dose reduction was achieved. After application of the mathematical filter, image noise was reduced by 45-80% for 100 mAs, and by 50-70% for 10 mAs scans. Only with a slice thickness of 1.25 mm, all lesions could be detected. The definition of lesion size and shape was more accurate with higher mAs. Only minor noise artifacts were noted on low-dose images. The automated polyp detector marked not more than 60% of artificial lesions. - CONCLUSION: MDCTC benefits from narrow slice collimation. In an in-vitro-model, a significant dose reduction is achievable with preservation of a high lesion detection rate. The noise reduction filter algorithm improved image quality substantially.

[Assessment of two different software solutions for the evaluation of CT colonography]. / Evaluation zwei verschiedener Softwarelösungen zur Auswertung von CT-Kolonographien.

PURPOSE: To compare a commercial CT colonography software ("Colonography", Siemens, Forchheim) with a non-commercial post-processing system ("Colotux", Department of Informatics). MATERIAL AND METHODS: Identical data sets of 10 patients, who underwent an ultra-low-dose multi-detector CT colonography (ULD-MDCTC) (4x1 mm collimation, 8 mm pitch, 120 kVp, 10 mAs) were analyzed retrospectively. Assessment was performed using both software solutions by two resident radiologists, who did not have any experience with any colonography software tool before and who did not know the clinical symptoms of the patients or the results of the conventional colonoscopy. Both systems were analyzed using several subjective quality criteria including workflow, handling, image quality, endoluminal navigation and analysis of lesions with grading on a 5-point-scale. Results concerning polyps were compared between the two systems as well as with conventional colonoscopy. RESULTS: Both colonography systems detected the same number of polyps. Although both showed some advantages for single criteria, no relevant difference was noted in general for subjective assessment. The time for calculation of three dimensional interactive volumes was three times longer for "Colotux" compared to "Colonography." Linux-based "Colotux" showed a trend towards better subjective image quality and easier measurement of polyp size. An intuitive desktop and "Syngo"-workflow integration were advantages of "Colonography." CONCLUSION: The analysis of CT colonographies (4-detector-row-CT-scanner, ultra low dose technique, supine position) can adequately be achieved by both software solutions. There was no significant subjective or objective difference of quality between a "stand-alone" individual system and a commercial workflow-integrated solution. A relevant factor for decision between the two systems may be the difference in time needed for the 3D volume calculation, especially in institutes with a high frequency of examinations.

Preserved verb generation in patients with cerebellar atrophy.

A role of the right cerebellar hemisphere has been suggested in linguistic functions. Nevertheless, studies of verb generation in cerebellar patients provide inconsistent results. The aim of the present study was to examine verb generation in a larger group of cerebellar patients with well-defined lesions. Ten subjects with degenerative cerebellar disorders and ten healthy matched controls participated. Subjects had to generate verbs to the blocked presentation of photographs of objects (i.e. four blocks of sixteen objects). As control condition, the objects had to be named. Furthermore, dysarthria was quantified by means of a sentence production and syllable repetition task. Volumetric analysis of individual 3D-MR scans was performed to quantify cerebellar atrophy. Cerebellar patients were slower in the sentence production and syllable repetition tasks, and cerebellar volume was decreased compared to controls. Despite cerebellar atrophy and dysarthria, the answers produced did not differ between patients and controls. In addition, both groups revealed the same amount of decrease in verbal reaction time over blocks (i.e. learning). The results suggest that the role of the cerebellum in verb generation is less pronounced than previously suggested.

Multi-slice CT-colonography in low-dose technique--Preliminary results.

PURPOSE: Assessment of Multi-Slice CT-colonography (MSCTC) with standard and low-dose technique in comparison to conventional colonoscopy (CC). MATERIALS AND METHODS: After standardized bowel cleansing, 28 men and 24 women (mean age 60,3 years) underwent CC within two hours after MSCTC had been performed (4 x 2.5 mm collimation, 3 mm slice width, 17.5 mm table feed, 120 kVp). In 19 patients, MSCTC was performed with 120 mAs (CTDI w, eff : 11.28 mGy), and in 33 patients with 10 mAs (CTDI w, eff : 0.94 mGy), respectively. After noise reduction using mathematical algorithms by a dedicated software (ECCET), images were analyzed by two blinded readers in simultaneously displayed 2D- and 3D-modes. Findings in MSCTC were compared to the results obtained with CC. RESULTS: Calculated effective doses ranged between 9 and 12 mSv for 120 mAs, and between 0.75 and 1 mSv for the low-dose technique. In standard dose MSCTC, 20 of 25 lesions (80 %) were found: all 7 tumors (100 %), one large polyp (> 10 mm; 100 %), 6 of 7 medium sized polyps (9.9 to 5 mm; 86 %) and 6 of 10 small polyps (< 5 mm; 60 %). In low-dose MSCTC, 32 of 44 lesions (73 %) were seen: all three large polyps (100 %), 13 of 14 medium sized polyps (93 %) and 16 of 27 small polyps (59 %). An overall sensitivity of 78 % with a specificity of 68 % was calculated. False positive findings were seen mostly for small lesions (12 for standard dose, 11 for low-dose). CONCLUSION: Despite a 12-fold reduction of radiation exposure, MSCTC in low-dose technique performs comparably well to standard dose MSCTC. After mathematical noise reduction, more than 90 % of polyps larger than 5 mm can be detected.

Adaptation to visuomotor rotation and force field perturbation is correlated to different brain areas in patients with cerebellar degeneration.

Although it is widely agreed that the cerebellum is necessary for learning and consolidation of new motor tasks, it is not known whether adaptation to kinematic and dynamic errors is processed by the same cerebellar areas or whether different parts play a decisive role. We investigated arm movements in a visuomotor (VM) rotation and a force field (FF) perturbation task in 14 participants with cerebellar degeneration and 14 age- and gender-matched controls. Magnetic resonance images were used to calculate the volume of cerebellar areas (medial, intermediate, and lateral zones of the anterior and posterior lobes) and to identify cerebellar structure important for the two tasks. Corroborating previous studies, cerebellar participants showed deficits in adaptation to both tasks compared with controls (P < 0.001). However, it was not possible to draw conclusions from the performance in one task on the performance in the other task because an individual participant could show severe impairment in one task and perform relatively well in the other (rho = 0.1; P = 0.73). We found that atrophy of distinct cerebellar areas correlated with impairment in different tasks. Whereas atrophy of the intermediate and lateral zone of the anterior lobe correlated with impairment in the FF task (rho = 0.72, 0.70; P = 0.003, 0.005, respectively), atrophy of the intermediate zone of the posterior lobe correlated with adaptation deficits in the VM task (rho = 0.64; P = 0.015). Our results suggest that adaptation to the different tasks is processed independently and relies on different cerebellar structures.

New angiographic measurement tool for analysis of small cerebral vessels: application to a subarachnoid haemorrhage model in the rat.

INTRODUCTION: Exact quantification of vasospasm by angiography is known to be difficult especially in small vessels. The purpose of the study was to develop a new method for computerized analysis of small arteries and to demonstrate feasibility on cerebral angiographies of rats acquired on a clinical angiography unit. METHODS: A new software tool analysing grey values and subtracting background noise was validated on a vessel model. It was tested in practice in animals with subarachnoid haemorrhage (SAH). A total of 28 rats were divided into four groups: SAH untreated, SAH treated with local calcium antagonist, SAH treated with placebo, and sham-operated. The diameters of segments of the internal carotid, caudal cerebral, middle cerebral, rostral cerebral and the stapedial arteries were measured and compared to direct measurements of the diameters on magnified images. RESULTS: There was a direct correlation between the cross-sectional area of vessels measured in a phantom and the measurements acquired using the new image analysis method. The spread of repeated measurements with the new software was small compared to the spread of direct measurements of vessel diameters on magnified images. Application of the measurement tool to experimental SAH in rats showed a statistically significant reduction of vasospasm in the SAH groups treated with nimodipine-releasing pellets in comparison to all the other groups combined. CONCLUSION: The presented computerized method for analysis of small intracranial vessels is a new method allowing precise relative measurements. Nimodipine-releasing subarachnoidal pellets reduce vasospasm, but further testing with larger numbers is necessary. The tool can be applied to human angiography without modification and offers the promise of substantial progress in the diagnosis of vasospasm after SAH.

Probabilistic 3D MRI atlas of the human cerebellar dentate/interposed nuclei.

In a previous study, a three-dimensional (3D) MRI atlas of the human cerebellar nuclei was introduced based on findings in one healthy human subject [Dimitrova, A., Weber, J., Redies, C., Kindsvater, K., Maschke, M., Kolb, F.P., Forsting, M., Diener, H.C., Timmann, D., 2002. MRI atlas of the human cerebellar nuclei. NeuroImage 17, 240-255]. The present MRI investigation was designed to study variability of the anatomy of the dentate/interposed nuclei in a larger group of healthy subjects. Similar to our previous study, iron-induced susceptibility artifacts were used to visualize the cerebellar nuclei as hypointensities on MR images. Data of 63 healthy subjects (27 female, 36 male; mean age 45.3+/-13.4 years, age range 22--71 years) were included. A 3D axial volume of the cerebellum was acquired using a T2*-weighted FLASH sequence on a Siemens Sonata 1.5 T MR scanner. Each volume was registered, re-sampled to 1.00 x 1.00 x 1.00 mm(3) voxel size and spatially normalized into a standard proportional stereotaxic space using SPM99. Dentate/interposed nuclei were traced on axial images and saved as regions of interest using MRIcro-software by two independent examiners. A probabilistic 3D MRI atlas of the cerebellar dentate/interposed nuclei is presented based on findings in all subjects.

Stimulus-response versus stimulus-stimulus-response learning in cerebellar patients.

Ample evidence exists that the cerebellum is involved in associative motor learning, particularly in eyeblink-conditioning. In visuomotor associative learning the role of the cerebellum is less clear. One open question is whether cerebellar patients' deficits in visuomotor learning are present both in a stimulus-response and a stimulus-stimulus-response association task. Twelve patients with cerebellar degeneration and 12 healthy matched control subjects participated. A magnetic resonance imaging (MRI) volumetric analysis of the cerebellum was performed to assess the degree of cerebellar atrophy. In a blocked design, subjects had to learn the association between one color square or two color squares and a right or left key press. In the latter condition, the two colors were shown one after the other in the same sequence except for two blocks at the end of the experiment. Overall, cerebellar subjects reacted significantly slower than controls. In both groups, reaction time decreased over blocks, and the learning effect was more pronounced in the stimulus-response than in the stimulus-stimulus-response condition. Post hoc analyses revealed that learning differences between conditions were significant in cerebellar patients but not control subjects. Furthermore, only healthy subjects were irritated, i.e., they significantly increased reaction times in the blocks with reversed sequence in the stimulus-stimulus-response condition. Cerebellar subjects tended to name less correct stimulus-stimulus-response associations after the experiment. Finally, cerebellar volume correlated with parameters of motor performance, but not learning. In conclusion, cerebellar patients showed deficits in stimulus-stimulus-response, but not stimulus-response learning. Future experiments are needed to differentiate between possible deficits in learning the stimulus-stimulus association, use of sequence information, and/or impaired motor performance interfering with learning.