Search

Background Pulmonary vein isolation (PVI) is at the forefront of treatment methods of rhythm control in patients with atrial fibrillation (AF) (1). The novel contact-force sensing catheter, QDot MicroTM (Biosense Webster) was designed to improve effectiveness of AF ablation and allow better time management due to shorter procedure time. It is a very high power-short duration (vHP-SD) catheter optimized for high density mapping and temperature control, which enables the application of high energy (up to 90W, 4s) (2). Purpose The aim of the study was to compare the QDot MicroTM catheter with the ThermoCool SmarttouchTM SF catheter with regard to the effectiveness and safety of PVI ablation. Methods It is a single center, cross-sectional, observational study enrolling 101 consecutive patients suffering from symptomatic paroxysmal or persistent AF, referred for first catheter ablation between 16 December 2019 and 03 December 2021. In 47 procedures (mean age 54 years; 70% male; 77% paroxysmal) the QDot Micro catheter was used (vHP-SD group; Qmode+ 90W, 4s), whereas the remaining 54 patients (mean age 57 years; 70% male; 67% paroxysmal) were treated with the ThermoCool SmarttouchTM SF catheter (control group, Ablation Index guided ablation). The primary endpoint was freedom from AF at 3-months after ablation. The secondary endpoints included the amount of opioids administered as well as the incidence of early-onset treatment-emergent adverse events (TEAEs). Results AF recurrence was documented in 14.9% patients in vHP-SD group and in 31.5% patients in control group (p=0.06). The mean dose of remifentanil was reported to be lower during Qmode+ catheter-based PVI (0.50 (0.40–0.60) vs. 0.70 (0.55–0.90) mg; p Conclusions This study suggests that the vHP-SD ablation is safe and enables sedative-analgesic medications demand reduction during procedure. vHP-SD mode may enhance the success rate of catheter-based PVI, however further research is needed to provide additional evidence of its superiority. Funding Acknowledgement Type of funding sources: None.

BACKGROUND: The prevalence of atrial fibrillation(AF) and diabetes mellitus is rising to epidemic proportions. We aimed to assess the impact of diabetes on the management and outcomes of patients with AF.METHODS: The EORP-AF General Long-Term Registry is a prospective, observational registry from 250 centres across 27 European countries. Outcomes of interest were as follows: i)rhythm control interventions; ii)quality of life; iii)healthcare resource utilisation; and iv)major adverse events.RESULTS: Of 11,028 patients with AF, the median age was 71 (63-77) years and 2537 (23.0%) had diabetes. Median follow-up was 24 months. Diabetes was related to increased use of anticoagulation but less rhythm control interventions. Using multivariable analysis, at 2-year follow-up, patients with diabetes were associated with greater levels of anxiety (p = 0.038) compared to those without diabetes. Overall, diabetes was associated with worse health during follow-up, as indicated by Health Utility Score and Visual Analogue Scale. Healthcare resource utilisation was greater with diabetes in terms of length of hospital stay (8.1 (±8.2) vs. 6.1 (±6.7) days); cardiology and internal medicine/general practitioner visits; and emergency room admissions. Diabetes was an independent risk factor of major adverse cardiovascular event (MACE; HR 1.26 [95% CI, 1.04-1.52]), all-cause mortality (HR 1.28 [95% CI, 1.08-1.52]), and cardiovascular mortality (HR 1.41 [95% CI, 1.09-1.83]).CONCLUSION: In this contemporary AF cohort, diabetes was present in 1 in 4 patients and it served as an independent risk factor for reduced quality of life, greater healthcare resource utilisation and excess MACE, all-cause mortality and cardiovascular mortality. There was increased use of anticoagulation therapy in diabetes but with less rhythm control interventions.

Funding Acknowledgements Type of funding sources: None. Introduction Ischemic mitral regurgitation (IMR) is predominantly related to left ventricle (LV) remodeling and mitral valve deformation. Although coronary artery bypass grafting alone (CABGa) or with mitral annuloplasty (CABGmp) is considered the best therapeutic strategies for patients with IMR, some recurrences are still reported. Purpose The aim of this study was to evaluate use of the mitral deformation indices (MDI) as a predictor of recurrence of IMR in 1-year follow-up after surgery. Methods A total of 145 patients after myocardial infarction with significant IMR, eligible for CABG, were prospectively enrolled in the study. Patients were referred for CABGa (gr.1; n = 90) or CABGmp (gr.2; n = 55), based on clinical assessment and the results of rest and stress echocardiography. One year after surgery each patient underwent the evaluation of cardiovascular events. Univariable logistic regression analysis was used to identify factors of recurrence of IMR in 1 year follow-up. Results Logistic regression analysis revealed that in CABGa group preoperative changes of TA and CH during DBX remained the predictors of the recurrence of IMR in 12 months follow-up. TAdbx > 1 cm2 provided sensitivity of 90% and specificity of 29%, (AUC 0.6436); The best cut-off value for CHdbx was 0.4 cm (sensitivity 90%, specificity 34%; AUC 0.6432). In both groups no significant differences were observed in 12-month mortality (1.2% vs 0%; p = 1.0), hospitalizations due to the heart failure (HF) exacerbation (5.9% vs 8.5%; p = 0.72) and in the incidence of the composite endpoint (deaths/CV hosp/stroke) (7% vs 8.5%; p = 0.742). Conclusion Preoperative assessment of MDI changes during dbx can be used to identify patients with IMR at increased risk of recurrence of significant IMR in 1 year follow-up. Abstract Figure 1 Abstract Figure 2

BACKGROUND: Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear.AIM: To assess the factors associated with cTn testing in routine practice and evaluate the association with outcomes.METHODS: Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into 3 groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), (iii) cTn elevated (>99th percentile). The composite outcome of any thromboembolism /any acute coronary syndrome/cardiovascular (CV) death, defined as Major Adverse Cardiovascular Events (MACE) and all-cause death were the main endpoints.RESULTS: Among 10 445 AF patients (median age 71 years, 40.3% females) cTn were tested in 2834 (27.1%). cTn was elevated in 904/2834 (31.9%) and in-range in 1930/2834 (68.1%) patients. Female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease, and atypical AF symptoms were independently associated with cTn testing. Elevated cTn were independently associated with a higher risk for MACE (Model 1, hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.40-2.16, Model 2, HR 1.62, 95% CI 1.28-2.05; Model 3 HR 1.76, 95% CI 1.37-2.26) and all-cause death (Model 1, HR 1.45, 95% CI 1.21-1.74; Model 2, HR 1.36, 95% CI 1.12-1.66; Model 3, HR 1.38, 95% CI 1.12-1.71).CONCLUSIONS: Elevated cTn levels were associated with an increased risk of all-cause mortality and adverse CV events. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

Purpose Allodynia refers to pain evoked by physiologically innocuous stimuli. It is a disabling symptom of neuropathic pain following a lesion within the peripheral or central nervous system. In fact, two different pathophysiological mechanisms of cold allodynia (ie, hypersensitivity to innocuous cold) have been proposed. The peripheral sensitization of nociceptive neurons can produce cold allodynia, which can be induced experimentally by a topical application of menthol. An alternative mechanism involves reduced inhibition of central pain processing by innocuous cold stimuli. A model to induce the latter type of allodynia is the conduction block of peripheral A-fiber input. Patients and methods In the presented study, functional MRI was used to analyze these two different experimental models of cold allodynia. In order to identify the underlying cerebral activation patterns of both mechanisms, the application of menthol and the induction of a mechanical A-fiber blockade were studied in healthy volunteers. Results The block-induced cold allodynia caused significantly stronger activation of the medial polymodal pain processing pathway, including left medial thalamus, anterior cingulate cortex, and medial prefrontal cortex. In contrast, menthol-induced cold allodynia caused significantly stronger activity of the left lateral thalamus as well as the primary and secondary somatosensory cortices, key structures of the lateral discriminative pathway of pain processing. Mean pain intensity did not differ between both forms of cold allodynia. Conclusion Experimental cold allodynia is mediated in different cerebral areas depending on the underlying pathophysiology. The activity pattern associated with block-induced allodynia confirms a fundamental integration between painful and non-painful temperature sensation, ie, the cold-induced inhibition of cold pain.

Background Focal hand dystonia has been associated with morphometric changes and distorted somatotopic representations in the putamen. Objective The authors used voxel-based morphometry (VBM) to identify regions in the putamen where grey-matter volume is associated with musician9s dystonia (MD) or the skill level of piano playing in professional pianists. Methods In 11 pianists with MD affecting the right hand and 12 healthy pianists without dystonia, the authors performed high-resolution T1-weighted MRI of the brain. The authors also measured the temporal variability of key strokes during scale playing with the right hand to characterise the individual skill level of piano playing. Statistical comparisons of the normalised and smoothed grey-matter maps were performed to test for dystonia and performance-related structural changes in the putamen. Results During scale playing, the timing of consecutive key strokes was more variable in MD patients than in non-dystonic pianists. Regional grey-matter volume in the middle part of left and right putamen increased with timing variability during piano playing in pianists with and without MD. Between-group comparisons revealed that MD patients had a larger grey-matter volume in the right middle putamen compared with healthy musicians. Conclusion In highly trained pianists with and without MD, the volume of the associative motor territory in the middle putamen reflects both the skill level of piano playing and the presence of dystonia. While a smaller volume is associated with better timing skills, a relative expansion is correlated with the presence of focal task-specific hand dystonia.

Here we review how transcranial magnetic stimulation (TMS) is used in clinical practice to examine the functional integrity of the fast conducting fibres of the human corticomotor pathways. We first summarise the technical and physiological principles of TMS that are relevant to its clinical use. We then discuss the neurophysiological measures that are used to characterise corticospinal conduction. Finally we present a step-by-step description of how to perform TMS in clinical practice.

Here we review the potential use of repetitive transcranial magnetic stimulation (rTMS) as a therapeutic intervention in patients with movement disorders. Most rTMS studies have been conducted in patients with Parkinson's disease (PD). Initially, rTMS was applied in a single session targeting the primary motor cortex (M1). In most single-session studies, rTMS was given after the discontinuation of dopaminergic medication. The majority of studies found a transient clinical improvement of motor symptoms after high-frequency (≥5 Hz) rTMS of the M1, especially when more than 1 000 stimuli had been applied. Recent studies applied multiple rTMS-sessions on several days and targeted multiple cortical sites. These studies provided preliminary evidence that the use of more extended stimulation protocols can prolong the therapeutic effects of high-frequency rTMS on parkinsonism. Inhibitory low-frequency (1 Hz) rTMS was found to be beneficial in some patients with focal hand dystonia, drug-induced dyskinesia, essential tremor, chorea, or tics. While these results are encouraging, the jury is still out whether this interventional technique will emerge as a routine treatment option in PD and other movement disorders. We discuss the challenges that still have to be faced when bringing rTMS treatment into regular clinical practice.

Objective: To investigate cerebellar gray matter volume in patients with essential tremor (ET). Methods: We used voxel-based morphometry (VBM) based on high-resolution T1-weighted MRI to compare gray and white matter density between 27 patients with ET and 27 age- and sex-matched healthy control subjects. Fourteen patients had only postural tremor, whereas 13 patients showed additional intention tremor. Results: VBM failed to demonstrate regional decreases in gray and white matter volume in patients with ET. There was, however, an expansion in gray matter depending on the type of tremor. Compared with age-matched control groups, patients with intention tremor showed a relative expansion of gray matter bilaterally in the region of the temporoparietal junction and the right middle occipital cortex. Conclusions: The lack of a consistent decrease in gray and white matter density argues against a progressive neurodegenerative process in essential tremor that leads to a substantial decrease in cerebellar gray matter volume. Patients with predominant intention tremor show a relative expansion of gray matter areas involved in higher order visuospatial processing, which might represent a long-term result of adaptive reorganization compensating the higher demands on the visuospatial control of skilled movements in case of trembling.

Contains fulltext : 48612.pdf (Publisher’s version ) (Closed access) We aimed to quantify the effects of bilateral subthalamic nucleus (STN) stimulation in Parkinson's disease (PD) on stance and gait ("axial"motor control), and related this to effects on finger movements ("appendicular" motor control). Fourteen PD patients and 20 matched controls participated. Subjects completed several balance and gait tasks (standing with eyes open or closed, on a normal or foam surface; retropulsion test; walking with eyes closed; walking up and down stairs; Get Up and Go test). Postural control was quantified using trunk sway measurements (angle and angular velocity) in the roll and pitch directions. Subjects further performed a pinch grip reaction time task, where we measured isometric grip forces, as well as movement and reaction times. Patients were examined with STN stimulators switched on or off (order randomised across patients), always after a supramaximal levodopa dosage. STN stimulation improved postural control, as reflected by a reduced trunk sway tremor during stance, a reduced duration for all gait tasks, an increased trunk pitch velocity while rising from a chair, and improved roll stability. STN stimulation also improved finger control, as reflected by a reduced time to reach maximum grip force, without altering reaction times and maximum force levels. Improvements in finger control timing did not correlate with reduced task durations during gait. We conclude that STN stimulation affords improvement of postural control in PD, over and above optimal drug treatment. STN stimulation also provides a simultaneous effect on distal and axial motor control. Because improvements in distal and axial motor control were not correlated, we assume that these effects are mediated by stimulation of different structures within the STN.

Objective: To examine the influence of the APOE e4 allele on cerebral glucose metabolism in a large series of patients with Alzheimer disease (AD). Methods: Eighty-three patients (41 APOE e4 positive and 42 e4 negative) were selected from a pre-existing databank of patients with AD (n > 1,000). The patients were carefully matched for age, age at onset, approximate disease duration, educational level, and overall degree of cognitive impairment. Cerebral [ 18 F]fluorodeoxyglucose PET imaging was performed in all patients by a standardized protocol. Statistical comparison of patient PET data vs a healthy control population was performed as well as an analysis of differences between groups (SPM99; Wellcome Department of Cognitive Imaging, London, UK). Results: A similar pattern of cerebral hypometabolism was detected in the e4-positive and -negative patient groups vs healthy volunteers in regions typically affected by AD (bilateral temporal, parietal, posterior cingulate, and prefrontal cortical areas). The comparison between e4-positive and -negative patients additionally revealed stronger abnormalities in e4 carriers in parietal, temporal, and posterior cingulate cortical regions. Conclusions: A generally similar pattern of cerebral hypometabolism was detected in APOE e4-positive and -negative patients with Alzheimer disease. However, in direct comparison of the two matched groups, the abnormalities in the e4-positive group were demonstrated to be more pronounced.

Der vorliegende Beitrag fasst potenzielle Anwendungsmoglichkeiten der Kombination von transkranieller Magnetstimulation (TMS) und funktioneller zerebraler Bildgebung zusammen. Die TMS erlaubt eine schmerzlose Stimulation eines umschriebenen Kortexareals. Die durch die TMS induzierte zerebrale Aktivierung kann mit funktionellen bildgebenden Verfahren dargestellt werden. Die Bildgebung kann hierbei entweder vor, wahrend oder nach der TMS zum Einsatz kommen. Die funktionelle Bildgebung vor einer geplanten TMS kann herangezogen werden, um den optimalen Stimulationsort fur die TMS zu definieren. Zudem kann mit der TMS nach funktioneller Bildgebung untersucht werden, welche funktionelle Relevanz eine regionale kortikale Aktivierung fur die Durchfuhrung einer bestimmten Aufgabe hat. Hierbei wird mit der TMS eine passagere Funktionsstorung des in der Bildgebung “aktivierten” Kortexareals induziert und untersucht, ob und wie die fokale TMS die Durchfuhrung der Aufgabe stort. Die funktionelle zerebrale Bildgebung wahrend der TMS erfasst die akuten Auswirkungen der TMS auf die Gehirnfunktion und erlaubt die In-vivo-Darstellung sowohl der regionalen kortikalen Exzitabilitat als auch der funktionellen intrazerebralen Konnektivitat des stimulierten Kortexareals. Die funktionelle zerebrale Bildgebung nach der TMS ist geeignet, die uberdauernden funktionellen Effekte der TMS auf die Gehirnfunktion zu erfassen. Dieser Ansatz bietet vielfaltige Moglichkeiten zur Erforschung funktioneller kortikaler Plastizitat und wird dazu beitragen, therapeutische Effekte der TMS besser zu verstehen.

Objective: Cerebral [ 18 F]fluorodeoxy-d-glucose PET ([ 18 F]FDG-PET) was used to visualize the lasting neuronal activation after repetitive transcranial magnetic stimulation (rTMS) over the left hand area of the primary motor cortex (M1 HAND ). Background: Applied over M1 HAND , rTMS has been shown to produce a modulation of corticomotor excitability beyond the time of stimulation itself. Methods: Eight right-handed subjects underwent nonquantitative [ 18 F]FDG-PET measurements during two experimental conditions: at rest and after focal subthreshold 5-Hz rTMS over the left M1 HAND . In the post-rTMS condition, [ 18 F]FDG was injected immediately after the administration of 1,800 magnetic pulses over the left M1 HAND . Relative differences in normalized regional cerebral metabolic rate of glucose (normalized rCMRglc) between conditions were determined using a voxel-by-voxel Student’s t -test and volume-of-interest (VOI) analysis. Analysis was a priori restricted to the M1 HAND , the supplementary motor area (SMA), and the primary auditory cortex of both hemispheres. Results: A 5-Hz rTMS of the left M1 HAND caused a lasting relative increase in normalized rCMRglc within the M1 HAND bilaterally and the SMA. The magnitude and the topographic pattern of persisting relative rCMRglc increases within these motor cortical areas demonstrated considerable interindividual variations. Conclusions: Subthreshold 5-Hz repetitive transcranial magnetic stimulation (rTMS) over the hand area of the primary motor cortex is associated with a persisting neuronal activation in a distinct set of motor cortical areas beyond the time of stimulation. The current findings demonstrate that [ 18 F]FDG-PET can localize and quantify regional net changes in synaptic cortical activity after rTMS and thus might elucidate the mechanisms underlying rTMS-associated therapeutic effects.

Positron emission tomography (PET) during focal repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising approach to study cortical connectivity in awake humans. However, the noise caused by the discharging magnetic coil might have confounding effects on the rTMS-related cortical activation pattern. In twelve healthy volunteers, 18-fluoro-2-deoxy-d-glucose (18FDG) PET was employed to visualize the functional activation of the primary auditory cortex (PAC) during 2 Hz rTMS of the left primary sensorimotor hand area. Magnetic stimuli (1800) were applied at an intensity of 140% of motor resting threshold during the uptake period of 18FDG. Though all subjects wore earplugs, rTMS-related noise induced a consistent bilateral increase of regional glucose utilization in the PAC (P

Using positron emission tomography (PET), we measured the relative changes in regional cerebral metabolic rate of glucose (rCMRglc) during 2 Hz repetitive transcranial magnetic stimulation (rTMS) of the left sensorimotor cortex (SM1) and during imitation of rTMS-induced arm movements. Such stimulation caused an rCMRglc increase of about 8% within the SM1. The relative rCMRglc increase within SM1 was significantly greater in magnitude and larger in area during voluntary imitation of rTMS-induced arm movements. Moreover, the rostral part of the SMA was significantly more activated by voluntary movements than during rTMS. Combining rTMS and PET has the potential to visualize rTMS-related net brain activation, and may open up new possibilities for functional network analysis by comparing willed brain activation with electromagnetic brain activation.

With respect to monitoring of high intensity focused ultrasound (HIFU), synonym focused ultrasound (FUS) treatment, magnetic resonance imaging (MRI) is characterized by several advantageous properties: the precise definition and morphological characterization of the target area (before and after the intervention), the real-time visualization of the treatment effect by thermal imaging (during the intervention) and in the sense of a stereotactic system, the 3-dimensional localization of the target lesion, planning of the target volume and assessment of the achieved ablation volume (before and during the intervention). Non-enhanced T2-weighted multislice MR images are acquired for planning of the intervention. For temperature monitoring (comprising thermometry and thermodosimetry), the temperature-dependent shift of proton resonance frequency (PRFS) is most frequently employed. This method is independent of the treated tissue type or thermally induced tissue changes and facilitates a relative measurement of the temperature change based on a reference value. Future MRI applications include diffusion-weighted MRI (DWI-MRI; for the intrainterventional estimation of treatment efficacy), dynamic contrast-enhanced MRI (DCE-MRI, for the prediction of the potential and assessment of the treatment effect achieved) and motion-corrected temperature monitoring (referenceless and multibaseline thermometry).

This article provides an overview of how transcranial magnetic stimulation (TMS) and positron emission tomography (PET) can be combined. It explains the methodology concerning the combination of TMS with PET and discusses the applications of this combination to study human brain function. TMS represents a nonphysiological means of producing or modulating neuronal activity in the human brain. PET imaging can make an important contribution to the understanding of the mechanisms of action of repetitive TMS and has the potential to determine neural correlates of compensatory plasticity in both healthy subjects and disease states. By using different sources of information, the TMS-PET approach provides insight into the neurophysiological effects of TMS on human brain function. The future use of TMS is to improve the understanding of how the nonphysiological mode of brain stimulation interacts with ‘normal’ activity in the human brain.

The aim of this study was to propose and evaluate a methodology to analyze simultaneously acquired T2*-weighted dynamic susceptibility contrast (DSC) MRI and T(1)-weighted dynamic contrast enhanced (DCE) MRI data. Two generalized models of T2*-relaxation are proposed to account for tracer leakage, and a two-compartment exchange model is used to separate tracer in intra- and extravascular spaces. The methods are evaluated using data extracted from ROIs in three mice with subcutaneously implanted human colorectal tumors. Comparing plasma flow values obtained from DCE-MRI and DSC-MRI data defines a practical experimental paradigm to measure T2*-relaxivities, and reveals a factor of 15 between values in tissue and blood. Comparing mean transit time values obtained from DCE-MRI and DSC-MRI without leakage correction, indicates a significant reduction of susceptibility weighting in DSC-MRI during tracer leakage. A one-parameter gradient correction model provides a good approximation for this susceptibility loss, but redundancy of the parameter limits the practical potential of this model for DSC-MRI. Susceptibility loss is modeled more accurately with a variable T2*-relaxivity, which allows to extract new parameters that cannot be derived from DSC-MRI or DCE-MRI alone. They reflect the cellular and vessel geometry, and thus may lead to a more complete characterization of tissue structure.

Objective To investigate whether movement-related cortical potentials (MRCP) provide a physiological correlate that indicates the response to treatment in patients with writer’s cramp. Methods In 21 patients with writer’s cramp, who underwent 4 weeks of limb immobilization followed by re-training for 8 weeks, we recorded MRCPs preceding a self-initiated brisk finger abduction movement. MRCP measurements of pre-movement activity were performed at baseline, after the end of immobilization and four and 8 weeks of re-training. We examined 12 controls, who received no intervention, twice 4 weeks apart. Results Patients benefited from the therapeutical intervention ( Zeuner et al., 2008 ). They showed no abnormalities of the MRCPs at baseline. In controls, MRCPs did not significantly change after 4 weeks. In patients, immobilization and re-training had no effect on MRCPs. There was no correlation between the severity of dystonic symptoms or the individual treatment response and MRCPs. Conclusion MRCPs are stable measures for interventional studies. However, they do not reflect clinical severity of dystonic symptoms or improvement after therapeutic interventions. Significance This is the first study to investigate MRCPs in a large cohort of patients with writer’s cramp compared to a control group at different time points. These potentials do not reflect the motor control disorder in patients with writer’s cramp.

In this paper a new piezo actuated drive the PAD is introduced. The PAD exhibits a combination of working principle and characteristics that makes it ideally suitable for robotics and positioning tasks in an MRI. Experiments in a 1.5 Tesla MRI showed that there is a high distortion in the images with the PAD next to the slice, but the image quality is improving rapidly, with an increasing distance between the PAD and the image by some centimeters. Connecting the PAD to the power supply does not affect the distortion, but increases the noise in the image.

Previous studies showed a beneficial effect of motor re-training in task-specific hand dystonia. Here we examined whether re-training needs to specifically focus on the task affected by dystonia. 21 patients with writer's cramp were randomly assigned to two types of re-training: One group of patients trained drawing and writing movements using a pen attached to the bottom of a finger splint. The second group used therapeutic putty to train finger movements without exercises of drawing and writing movements. Training lasted for eight weeks. Before re-training, affected hand and forearm were immobilized for four weeks to facilitate the responsiveness to re-training. Dystonia was assessed during handwriting using the Writer's Cramp Rating Scale. While no clinical improvement was observed immediately after immobilization, eight weeks of re-training improved task-specific dystonia relative to baseline (p=0.005). Both training modalities were equally effective. More severely affected patients benefited most. There was no correlation between disease duration and the individual treatment response. Re-training also improved hand function as indexed by the Arm Dystonia Disability Scale (p=0.008). Kinematic handwriting analysis showed that re-training lowered vertical force level and enhanced the fluency of handwriting. We conclude that re-training does not need to specifically focus on the task affected by dystonia to be clinically effective.

Functional neuroimaging studies have identified a set of areas in the intraparietal sulcus and dorsal precentral cortex which show a linear increase in activity with the angle of rotation across a variety of mental rotation tasks. This linear increase in activity with angular disparity suggests that these frontoparietal regions compute rotational transformations. An open question is whether rotated target stimuli automatically activate these frontoparietal regions, even if the task does not require rotational transformations. To address this question, we performed functional MRI while healthy male volunteers made two-choice reaction-time judgements on canonical or mirror images of two-dimensional alphanumeric characters presented at various angles of rotation. Participants had either to decide whether characters were normal or mirror-reversed (i.e., mental rotation) or judge whether the stimulus was a letter or a number (i.e., stimulus categorization). Reaction times and error rates linearly increased with the angle of rotation for mirror-reversed judgements but not for number–letter judgements, showing that only the mental rotation task required rotational transformations of the characters. The mental rotation task was associated with a linear increase in neuronal activity with angular disparity in a bilateral set of frontoparietal areas, comprising the rostral dorsal premotor cortex, frontal eye field, ventral and medial intraparietal sulcus. Neuronal activity in these regions was neither increased nor modulated by angular disparity during the stimulus categorization task. These results suggest that at least for alphanumerical characters, areas implicated in mental rotation will only be called into action if the task requires a rotational transformation.

Purpose: To our knowledge, there are no published data pertinent to the use of [F-18]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in patients with natural killer (NK)/T-cell lymphoma. The purpose of this study was to assess the value of FDG PET/CT in this aggressive type of non-Hodgkin lymphoma. Patients and Methods: All patients with NK/T-cell lymphoma referred for FDG PET/CT at our institution from July 2001 to July 2006 were retrospectively studied. PET/CT examinations were blindly reviewed by 2 experienced readers. The results were compared with the status of the disease, which was determined after evaluation of biopsy, laboratory, clinical and conventional imaging examination, and follow-up results. PET/CT results were thereby classified as true-positive, true-negative, false-positive, or false-negative. The degree of FDG uptake in the positive lesions was semiquantified using maximum standard uptake value (SUVmax). Results: Twenty-one PET/CT examinations were performed in 10 patients with NK/T-cell lymphoma. For nasal disease, PET/CT was true-positive in 5 cases, true-negative in 15 cases, and positive but unconfirmed in 1 case. For extranasal disease, PET/CT was true-positive in 3 cases, true-negative in 16 cases, and false-negative in 2 cases. The mean SUVmax in PET-positive lesions in nasal cavities or paranasal sinuses was 16 gm/mL (range, 5-25 gm/mL; median, 19.3 gm/mL). In extranasal disease, the mean SUVmax was 10.9 gm/mL (range, 4.6-34.1 gm/mL; median, 5.6 gm/mL). Conclusion: Viable NK/T-cell lymphoma is intensely FDG hypermetabolic. PET/CT appears to be sensitive for the detection of disease in the nasopharynx and, to a lesser extent, in extranasal sites.

Background: In patients with Parkinson disease (PD), transcranial magnetic stimulation (TMS) studies have consistently demonstrated a reduced inhibitory tone in the sensorimotor cortex. It remains unclear whether this is related to motor symptoms or represents adaptive compensatory changes to degeneration of dopaminergic neurons. Here we used short-interval afferent inhibition after digital stimulation (dSAI) and intracortical paired-pulse inhibition and facilitation to probe intracortical sensorimotor excitability in clinically asymptomatic carriers of a single mutant Parkin allele who have a latent nigrostriatal dopaminergic dysfunction.Methods: Nine heterozygous mutation carriers and nine healthy controls were investigated. For dSAI testing, electrical pulses were applied to the right index finger followed by TMS pulses over the left motor cortex at interstimulus intervals (ISI) of 25, 30, and 40 msec. Intracortical paired-pulse excitability was tested at ISIs of 2 to 15 msec.Results: dSAI was reduced at an ISI of 25 msec in carriers of a single mutant Parkin allele, whereas paired-pulse TMS was normal.Conclusion: The relative decrease in sensorimotor inhibition may be a direct consequence of the Parkin mutation or represent adaptive changes at the cortical level in response to a subcortical dysfunction, but is not caused by motor symptoms.

Aufgrund der engen raumlich-zeitlichen Kopplung von regionalem zerebralem Blutfluss, Glukosestoffwechsel und synaptischer Aktivitat liefert die Positronenemissionstomografie (PET) des regionalen zerebralen Blutflusses oder der regionalen Glukoseaufnahme ein Abbild des regionalen zerebralen Aktivierungszustands zum Zeitpunkt der PET-Messung (Exkursbox »Positronenemissionstomografie«). Neben der metabolischen Bildgebung zur Darstellung der regionalen synaptischen Nettoaktivitat kann die PET zusatzliche Aspekte menschlicher Hirnfunktion darstellen, die bislang weder der funktionellen MRT noch der EEG zuganglich sind. So stehen fur die PET Radioliganden zur Verfugung, mit denen die Effekte der TMS auf spezifische Neurotransmittersysteme (z. B. das dopaminerge System) oder Zellpopulationen (z. B. Mikroglia) untersucht werden konnen (Exkursbox »Positronenemissionstomografie«). All diese PET-Untersuchungsverfahren eroffnen in der Kombination mit der TMS wertvolle Einblicke in die Wirkweise der TMS und die funktionelle Neuroanatomie des menschlichen Gehirns.

Fragestellung: Die pathophysiologische Bedeutung des Kleinhirns beim klassischen essentiellen Tremor (ET) wurde anhand klinischer, elektrophysiologischer und funktionell-bildgebender Verfahren belegt. Unklar ist derzeit, ob die cerebellare Dysfunktion auch mit subtilen strukturellen Auffalligkeiten des cortico-cerebello-thlamischen Symstems assoziiert ist. Methoden: Wir fuhrten eine voxelbasierte Morphometrie (VBM) der grauen und weisen Hirnsubstanz basierend auf hochauflosenden T1-gewichteten MRT-Sequenzen durch. Untersucht wurden 27 Patienten mit ET und 27 in Alter und Geschlecht vergleichbare Kontrollpersonen. Unter den ET-Patienten befanden sich 14 Patienten mit einem posturalen Tremor und 13 Patienten mit einem zusatzlichen Intentionstremor. Ergebnisse: Es liesen sich keine signifikanten Unterschiede in der Dichte der grauen und weisen Substanz zwischen ET-Patienten und Kontrollpersonen nachweisen. Dieses galt auch, wenn die ET-Untergruppen (mit und ohne Intentionstremor) separat mit den entsprechenden Kontrollpersonen verglichen wurden. Der Vergleich beider Patientenuntergruppen jedoch zeigte bei ET-Patienten mit Intentionstremor eine relative Zunahme in der Dichte der grauen Substanz beiderseits im Bereich des temporoparietalen Ubergangs und des rechten Gyrus occipitalis medialis. Schlussfolgerungen: Es ergab sich kein Hinweis auf einen neurodegenerativen Prozess als Ursache des ET. Patienten mit Intentionstremor zeigen eine relative Vermehrung der grauen Substanz in Hirnarealen, die in visuell-raumliche Verarbeitungsprozesse involviert sind, wobei es sich hier um eine ausbleibende physiologische Volumenabnahme im Alter zu handeln scheint. Diese lokal ausbleibende Hirnatrophie ware als adaptive Reorganisation bei langfristiger hoher Beanspruchung der fur die visuell-raumliche Kontrolle zielgerichteter Bewegungen zustandigen Systeme durch den Tremor zu sehen.

Writer's cramp is a task-specific hand dystonia affecting handwriting. Clinical scores such as the Arm Dystonia Disability Scale (ADDS) or Writer's Cramp Rating Scale (WCRS) as well as kinematic analysis of handwriting movements have been used to assess functional impairment in affected patients. In 21 patients with writer's cramp and healthy controls, we analyzed the kinematics of writing and cyclic drawing movements. We rated the severity of dystonia using the ADDS and WCRS and correlated the clinical scores with movement kinematics. Mean stroke frequency was significantly reduced in dystonic patients. Drawing movements showed more frequently a decrease in stroke frequency than handwriting movements. During circle drawing, mean vertical peak velocity was more variable in patients relative to controls, indicating an impaired ability to reproduce the same kinematic pattern over time. An increase in vertical writing pressure was only observed during handwriting but not during circle drawing and may reflect a compensatory effort to stabilize the pencil. Kinematic measures and individual ADDS and WCRS scores did not correlate with each other. The lack of correlation is not surprising as ADDS, WCRS, and kinematic analysis probe different aspects of motor impairment. The ADDS characterizes how dystonia affects a set of fine manual tasks, whereas the WCRS scores the manifestation of dystonia during handwriting. Therefore, the clinical scores and kinematic analysis of handwriting provide complementary insights into motor impairment. Future studies need to address which combination of clinical scores and kinematic measures are most appropriate to quantify impairment in writer's cramp.

Writer's cramp is a focal hand dystonia that specifically affects handwriting. Though writer's cramp has been attributed to a dysfunction of the basal ganglia, the role of the basal ganglia in the pathogenesis of writer's cramp remains to be determined. Seventeen patients with writer's cramp (nine females; age range: 24-71 years) and 17 healthy individuals (six females; age range: 27-68 years) underwent functional MRI (fMRI) while they discriminated the orientation of gratings delivered to the tip of the right index finger. Statistical parametric mapping was used to analyse the fMRI data. The significance level was set at a corrected P-value of 0.05. Relative to healthy controls, patients with writer's cramp showed a widespread bilateral increase in task-related activity in the putamen, caudate nucleus, internal globus pallidus and lateral thalamus. In these areas, hyperactivity was more pronounced in patients who had recently developed writer's cramp. The enhanced response of the basal ganglia to tactile input from the affected hand is compatible with the concept of impaired centre-surround inhibition within the basal ganglia-thalamic circuit and may lead to an excessive activation of sensorimotor cortical areas during skilled movements affected by dystonia. Outside the basal ganglia, dystonic patients showed task-related overactivity in visual cortical areas, left anterior insula and right intraparietal sulcus, but not in the primary or secondary sensory cortex. In addition, task-related activity in the cerebellar nuclei, posterior vermis, right paramedian cerebellar hemisphere and dorsal pons was inversely related with the severity of hand dystonia. Regional activity in these areas may reflect secondary adaptive reorganization at the systems level to compensate for the dysfunction in the basal ganglia-thalamic loop.

In oxygen-enhanced lung MRI, difference maps of acquisitions during inhalation of room air and pure oxygen are calculated to assess lung function. The purpose of this study was to analyze how the calculation of these difference maps depends on the delayed signal change after switching the gas supply.Ten healthy volunteers were examined with an ECG and respiratory-triggered T1-weighting inversion recovery HASTE sequence with parallel imaging. Four blocks with 20 repetitions of up to 6 coronal slices were continuously acquired; in blocks 1 and 3 room air was supplied, in blocks 2 and 4 oxygen. Data were postprocessed, discarding between 0 and 19 repetitions after each change of gas supply before calculating the relative signal difference.The averaged relative signal difference increases from 9.4 to 17.4% when the number of discarded acquisitions increases; the ratio of signal difference and spatial standard deviation reaches a maximum at 5-8 discarded acquisitions.An optimized ratio of signal difference and statistical error is found if about 5-8 of 20 respiratory-triggered repetitions are discarded after each change of gas supply for the calculation of difference maps.

Background Successful cognitive performance depends not only on the activation of specific neuronal networks but also on selective suppression of task-irrelevant modalities, i.e., deactivation of non-required cerebral regions. This ability to suppress the activation of specific brain regions has, to our knowledge, never been systematically evaluated in patients with Alzheimer disease (AD). The aim of the current study was to evaluate both cerebral activation and deactivation in (1) healthy volunteers, (2) patients with mild cognitive impairment (MCI) who are at risk for AD, and (3) patients with moderate AD during active navigation, representing a cognitive task typically affected in AD. Methods and Findings Changes in regional cerebral blood flow (rCBF) were assessed with PET imaging during an active navigation task in a 3D virtual-reality environment. The task was based on visual cues exclusively; no auditory cues were provided. Age-matched groups of healthy individuals, patients with MCI, and patients with AD were examined. Specific differences in the activation patterns were observed in the three groups, with stronger activation of cerebellar portions and visual association cortex in controls and stronger activation of primary visual and frontal cortical areas in patients with MCI and AD. Highly significant bilateral decrease of rCBF in task-irrelevant auditory cortical regions was detected in healthy individuals during performance of the task. This rCBF decrease was interpreted as a cross-modal inhibitory effect. It was diminished in patients with MCI and completely absent in patients with AD. A regression analysis across all individuals revealed a clear positive relation between cognitive status (mini mental state examination score) and the extent of auditory cortical deactivation. Conclusion During active navigation, a high level of movement automation and an involvement of higher-order cerebral association functions were observed in healthy controls. Conversely, in patients with MCI and AD, increased cognitive effort and attention towards movement planning, as well as stronger involvement of lower-order cerebral systems, was found. Successful cognitive performance in healthy individuals is associated with deactivation of task-irrelevant cerebral regions, whereas the development of AD appears to be characterized by a progressive impairment of cross-modal cerebral deactivation functions. These changes may cause the generally decreased ability of patients with AD to direct attention primarily to the relevant cognitive modality., When performing a navigation task with exclusively visual clues, healthy individuals de-activate areas of the brain involved in hearing. In individuals with Alzheimer Disease, no deactivation is seen.

To demonstrate the potential of quantitative MRI-assisted thermometry for the treatment of tumor patients with regional hyperthermia (RHT) and interstitial laser thermotherapy (ILTT).Two patients and seven tissue samples were investigated using the T1-relaxation time and the chemical shift of the proton resonance frequency (PRF) as temperature sensitive MRI-parameters at 0.2 and 1.5 T. Thermotherapy was applied using either a dedicated MRI-hyperthermia hybrid system or a temperature controlled laser with 830 nm.Both patients were treated successfully showing clinical benefit. T1 and PRF are depending on the applied thermotherapy method and on the MR-system suitable for MRI-assisted thermometry. The clinical application based on phantom results is not necessarily adequate.Clinical application and phantom experiments of RHT and ILTT show the potential of MRI-assisted thermometry for further improvement of both minimal invasive thermotherapy methods. Further investigations concerning optimization of the MRI-techniques, the influence of perfusion or the determination of threshold values are necessary.

Publisher Summary This chapter focuses on the combination of transcranial magnetic stimulation (TMS) with positron emission tomography (PET) imaging of regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of glucose (rCMRglc). Despite limited temporal and spatial resolution, the combination of PET with TMS offers some methodological advantages over combined TMS–fMRI studies. Compared with TMS in the MRI scanner, the prerequisites for applying TMS in the PET scanner are relatively easy to establish. PET measurements give an estimate of regional synaptic activity over several tens of seconds or minutes. Combined TMS–PET studies can use the limited temporal resolution of PET as an advantage because a single PET scan will represent the summation of the effects of individual stimuli on regional synaptic activity. The major advantage of PET is that it is possible to make direct comparisons of synaptic activity among different scanning sessions. This makes PET ideally suited to comparing changes in activity because of different TMS paradigms performed on separate days.

The present paper aims to summarize potential applications of transcranial magnetic stimulation (TMS) combined with functional brain imaging. Transcranial magnetic stimulation is a well-established noninvasive tool for stimulating circumscribed areas of the human cortex. Functional imaging techniques such as positron emission tomography, functional magnetic resonance imaging, and electroencephalographic mapping enable assessment of TMS-related functional brain activation. A combination of TMS and functional imaging can be useful in three principal ways. (1) Brain imaging before TMS is helpful in defining the accurate coil position over a distinct cortical area which is targeted by TMS. Since TMS can be used to interfere with regional cortical function during a given task, the effects of focal TMS on task performance can help to clarify the task-specific functional contribution of a given cortical area which has previously shown task-related activation in a functional imaging study. (2) Imaging the brain during TMS is a promising approach for assessing cortical excitability and intracerebral functional connectivity. (3) By evaluating lasting effects of TMS, brain imaging after TMS can be employed to study the plasticity of the human cortex. Moreover, this approach will help to advance our understanding of therapeutical effects related to TMS.

The behavior of the signal intensity in MRI of human lungs was investigated during inhalation of pure oxygen. Nine volunteers were examined, five using a breath-hold and four using a non-breath-hold technique. Four coronal slices were acquired in each volunteer using an inversion recovery turbo spin-echo sequence. The inversion time of the sequence was optimized for maximum contrast. Breathing of pure oxygen and room air was alternated in the volunteers. Breath-hold and non-breath-hold cases were compared. Breathing pure oxygen lead to a statistically significant signal intensity increase (up to 18%) compared to breathing room air. In addition, T(1) maps were acquired during breathing 100% oxygen and room air. Inhalation of pure oxygen reduced the mean T(1) time of the lungs from 1280 (+/-85) msec to 1224 (+/-139) msec without breath-hold and from 1219 (+/-176) to 1074 (+/-92) msec with breath-hold. Therefore, an optimized sequence and measurement protocol provided significant signal intensity changes utilizing 100% oxygen. Magn Reson Med 43:860-866, 2000.