Search tips
Search criteria

Results 1-12 (12)

Clipboard (0)

Select a Filter Below

Year of Publication
1.  Correlation between Relaxometry and Diffusion Tensor Imaging in the Globus Pallidus of Huntington’s Disease Patients 
PLoS ONE  2015;10(3):e0118907.
Huntington's disease (HD) is an inherited neurodegenerative disorder with progressive impairment of motor, behavioral and cognitive functions. The clinical features of HD are closely related to the degeneration of the basal ganglia, predominantly the striatum. The main striatal output structure, the globus pallidus, strongly accumulates metalloprotein-bound iron, which was recently shown to influence the diffusion tensor scalar values. To test the hypothesis that this effect dominates in the iron-rich basal ganglia of HD patients, we examined the globus pallidus using DTI and T2 relaxometry sequences. Quantitative magnetic resonance (MR), clinical and genetic data (number of CAG repeats) were obtained from 14 HD patients. MR parameters such as the T2 relaxation rate (RR), fractional anisotropy (FA) and mean diffusivity (MD) were analysed. A positive correlation was found between RR and FA (R2=0.84), between CAG and RR (R2=0.59) and between CAG and FA (R2=0.44). A negative correlation was observed between RR and MD (R2=0.66). A trend towards correlation between CAG and MD was noted. No correlation between MR and clinical parameters was found. Our results indicate that especially magnetic resonance FA measurements in the globus pallidus of HD patients may be strongly affected by metalloprotein-bound iron accumulation.
PMCID: PMC4362949  PMID: 25781024
2.  Magnetic resonance imaging in patients with a subcutaneous implantable cardioverter-defibrillator 
Europace  2015;17(5):761-766.
Our aim was to evaluate the potential for safely imaging patients with a new type of implantable cardioverter-defibrillator called the subcutaneous implantable cardioverter-defibrillator (S-ICD) in a 1.5 T magnetic resonance imaging (MRI) scanner. With the increasing number of patients with cardiac implantable devices who are indicated for MRI, there is a growing need for establishing MRI compatibility of cardiac implantable devices.
Methods and Results
Patients with implanted S-ICD systems underwent one or more types of anatomical MRI scans. The S-ICD was programmed off and patients were monitored throughout the imaging procedure. Device function was evaluated pre- and post-scan. Patients were asked to report immediately any pain, torqueing movement, or heating sensation in the area of the pocket or electrode. Fifteen patients underwent a total of 22 examinations at 1.5 T. Scans included brain, spine, knee, and heart. Two patients were re-scanned due to complaints of heating over the can during lumbar scans, which was caused by a thermistor probe placed on the skin to measure skin temperature. All the remaining scans occurred without incident. No evidence of device malfunction was observed.
This study is the first to domonstrate the feasibility of exposing S-ICD patients to MRI using the scanning and monitoring protocol described. More data are required to support S-ICD as a MRI conditional device.
PMCID: PMC4413883  PMID: 25687749
Implantable defibrillator; Subcutaneous S-ICD; Magnetic resonance imaging
3.  Alterations in the basal ganglia in patients with brain tumours may be due to excessive iron deposition 
Oncology Letters  2014;9(1):43-46.
The accumulation of iron in the brain is a common physiological process. However, alterations in the deposition of iron or other paramagnetic substances are associated with various diseases. In the present study, the deposition of paramagnetic substances in patients with brain tumours was evaluated using T2 relaxometry. A total of 23 patients with untreated tumours or with recurrent tumours following treatment, together with a group of 19 age-matched healthy controls, were examined using T2 relaxometry at 3T. The relaxation times in the basal ganglia, thalamus and white matter were evaluated. Significantly lower T2 relaxation times were identified in the basal ganglia and thalamus of the patients with tumours, as compared with those of the controls (P<0.05). No statistically significant difference was identified between patients with untreated or recurrent brain tumours. The reduction in T2 relaxation times in the brain tumour patients was possibly caused by the accumulation of iron, since iron homeostasis is known to be altered in patients with tumours. We propose that increased iron deposition is a consequence of a higher risk of oxidative stress caused by an increased iron concentration in the plasma or cerebrospinal fluid.
PMCID: PMC4246608  PMID: 25435931
magnetic resonance imaging; brain tumours; basal ganglia; iron; oxidative stress
4.  New Non-Linear Color Look-Up Table for Visualization of Brain Fractional Anisotropy Based on Normative Measurements – Principals and First Clinical Use 
PLoS ONE  2013;8(8):e71431.
Fractional anisotropy (FA) is the most commonly used quantitative measure of diffusion in the brain. Changes in FA have been reported in many neurological disorders, but the implementation of diffusion tensor imaging (DTI) in daily clinical practice remains challenging. We propose a novel color look-up table (LUT) based on normative data as a tool for screening FA changes. FA was calculated for 76 healthy volunteers using 12 motion-probing gradient directions (MPG), a subset of 59 subjects was additionally scanned using 30 MPG. Population means and 95% prediction intervals for FA in the corpus callosum, frontal gray matter, thalamus and basal ganglia were used to create the LUT. Unique colors were assigned to inflection points with continuous ramps between them. Clinical use was demonstrated on 17 multiple system atrophy (MSA) patients compared to 13 patients with Parkinson disease (PD) and 17 healthy subjects. Four blinded radiologists classified subjects as MSA/non-MSA. Using only the LUT, high sensitivity (80%) and specificity (84%) were achieved in differentiating MSA subjects from PD subjects and controls. The LUTs generated from 12 and 30 MPG were comparable and accentuate FA abnormalities.
PMCID: PMC3750032  PMID: 23990954
5.  Motor Matters: Tackling Heterogeneity of Parkinson’s Disease in Functional MRI Studies 
PLoS ONE  2013;8(2):e56133.
To tackle the heterogeneity of Parkinson’s disease symptoms, most functional imaging studies tend to select a uniform group of subjects. We hypothesize that more profound considerations are needed to account for intra/inter-subject clinical variability and possibly for differing pathophysiological processes. Twelve patients were investigated using functional magnetic resonance imaging during visually-guided finger tapping. To account for disease heterogeneity, the motor score and individual symptom scores from the Unified Parkinson’s Disease Rating Scale (UPDRS-III) were utilized in the group-level model using two approaches either as the explanatory variable or as the effect of interest. Employment of the UPDRS-III score and symptom scores was systematically tested on the resulting group response to the levodopa challenge, which further accentuated the diversity of the diseased state of participants. Statistics revealed a bilateral group response to levodopa in the basal ganglia. Interestingly, systematic incorporation of individual motor aspects of the disease in the modelling amended the resulting activity patterns conspicuously, evidencing a manifold amount of explained variability by the particular score. In conclusion, the severity of clinical symptoms expressed in the UPDRS-III scores should be considered in the analysis to attain unbiased statistics, draw reliable conclusions and allow for comparisons between research groups studying Parkinson’s disease using functional magnetic resonance imaging.
PMCID: PMC3572025  PMID: 23418522
6.  The Subthalamic Microlesion Story in Parkinson's Disease: Electrode Insertion-Related Motor Improvement with Relative Cortico-Subcortical Hypoactivation in fMRI 
PLoS ONE  2012;7(11):e49056.
Electrode implantation into the subthalamic nucleus for deep brain stimulation in Parkinson's disease (PD) is associated with a temporary motor improvement occurring prior to neurostimulation. We studied this phenomenon by functional magnetic resonance imaging (fMRI) when considering the Unified Parkinson's Disease Rating Scale (UPDRS-III) and collateral oedema. Twelve patients with PD (age 55.9± (SD)6.8 years, PD duration 9–15 years) underwent bilateral electrode implantation into the subthalamic nucleus. The fMRI was carried out after an overnight withdrawal of levodopa (OFF condition): (i) before and (ii) within three days after surgery in absence of neurostimulation. The motor task involved visually triggered finger tapping. The OFF/UPDRS-III score dropped from 33.8±8.7 before to 23.3±4.8 after the surgery (p<0.001), correlating with the postoperative oedema score (p<0.05). During the motor task, bilateral activation of the thalamus and basal ganglia, motor cortex and insula were preoperatively higher than after surgery (p<0.001). The results became more enhanced after compensation for the oedema and UPDRS-III scores. In addition, the rigidity and axial symptoms score correlated inversely with activation of the putamen and globus pallidus (p<0.0001). One month later, the OFF/UPDRS-III score had returned to the preoperative level (35.8±7.0, p = 0.4).
In conclusion, motor improvement induced by insertion of an inactive electrode into the subthalamic nucleus caused an acute microlesion which was at least partially related to the collateral oedema and associated with extensive impact on the motor network. This was postoperatively manifested as lowered movement-related activation at the cortical and subcortical levels and differed from the known effects of neurostimulation or levodopa. The motor system finally adapted to the microlesion within one month as suggested by loss of motor improvement and good efficacy of deep brain stimulation.
PMCID: PMC3492182  PMID: 23145068
7.  Long-term survival of patients suffering from glioblastoma multiforme treated with tumor-treating fields 
Glioblastoma multiforme (GBM) is the most common and malignant primary intracranial tumor, and has a median survival of only 10 to 14 months with only 3 to 5% of patients surviving more than three years. Recurrence (RGBM) is nearly universal, and further decreases the median survival to only five to seven months with optimal therapy. Tumor-treating fields (TTField) therapy is a novel treatment technique that has recently received CE and FDA approval for the treatment of RGBM, and is based on the principle that low intensity, intermediate frequency electric fields (100 to 300 kHz) may induce apoptosis in specific cell types. Our center was the first to apply TTField treatment to histologically proven GBM in a small pilot study of 20 individuals in 2004 and 2005, and four of those original 20 patients are still alive today. We report two cases of GBM and two cases of RGBM treated by TTField therapy, all in good health and no longer receiving any treatment more than seven years after initiating TTField therapy, with no clinical or radiological evidence of recurrence.
PMCID: PMC3514151  PMID: 23095807
Glioblastoma multiforme; Recurrent glioblastoma multiforme; Tumor-treating fields; Long-term survival
8.  Comparison of CT and MR imaging in ischemic stroke 
Insights into Imaging  2012;3(6):619-627.
Cerebrovascular disease represents a major source of global mortality and morbidity. Imaging examinations play a critical role in the management of stroke patients, from establishing the initial diagnosis to determining and guiding further treatment.
In this article, current CT and MRI methods employed in the management of stroke patients are reviewed, with an emphasis on ischemic stroke.
The advantages and disadvantages of these techniques are discussed, a number of cases emphasizing key points are presented, and a comparison between modern CT and MRI techniques is outlined.
The major drawback of CT is the high radiation dose, while in MRI it is the more complicated and time-consuming aspect of the examination.
Main Messages
• Cerebrovascular disease represents a major source of global mortality and morbidity
• Imaging examinations play a critical role in the management of stroke patients
• The penumbra may be seen with both CT and MRI; however, this concept may be overly simplistic
• The major drawback of CT is the high radiation dose, while MRI is a more complicated examination
PMCID: PMC3505566  PMID: 23055115
Cerebrovascular stroke; Magnetic resonance imaging; Computed tomography, spiral; Perfusion imaging
9.  Weight Gain Is Associated with Medial Contact Site of Subthalamic Stimulation in Parkinson's Disease 
PLoS ONE  2012;7(5):e38020.
The aim of our study was to assess changes in body-weight in relation to active electrode contact position in the subthalamic nucleus. Regular body weight measurements were done in 20 patients with advanced Parkinson's disease within a period of 18 months after implantation. T1-weighted (1.5T) magnetic resonance images were used to determine electrode position in the subthalamic nucleus and the Unified Parkinson's disease rating scale (UPDRS-III) was used for motor assessment. The distance of the contacts from the wall of the third ventricle in the mediolateral direction inversely correlated with weight gain (r = −0.55, p<0.01) and with neurostimulation-related motor condition expressed as the contralateral hemi-body UPDRS-III (r = −0.42, p<0.01). Patients with at least one contact within 9.3 mm of the wall experienced significantly greater weight gain (9.4±(SD)4.4 kg, N = 11) than those with both contacts located laterally (3.9±2.7 kg, N = 9) (p<0.001). The position of the active contact is critical not only for motor outcome but is also associated with weight gain, suggesting a regional effect of subthalamic stimulation on adjacent structures involved in the central regulation of energy balance, food intake or reward.
PMCID: PMC3364196  PMID: 22666437
10.  Abnormal Activity in the Precuneus during Time Perception in Parkinson's Disease: An fMRI Study 
PLoS ONE  2012;7(1):e29635.
Parkinson's disease (PD) patients are deficient in time estimation. This deficit improves after dopamine (DA) treatment and it has been associated with decreased internal timekeeper speed, disruption of executive function and memory retrieval dysfunction.
The aim of the present study was to explore the neurophysiologic correlates of this deficit. We performed functional magnetic resonance imaging on twelve PD patients while they were performing a time reproduction task (TRT). The TRT consisted of an encoding phase (during which visual stimuli of durations from 5s to 16.6s, varied at 8 levels were presented) and a reproduction phase (during which interval durations were reproduced by a button pressing). Patients were scanned twice, once while on their DA medication (ON condition) and once after medication withdrawal (OFF condition). Differences in Blood-Oxygenation-Level-Dependent (BOLD) signal in ON and OFF conditions were evaluated. The time course of activation in the brain areas with different BOLD signal was plotted. There were no significant differences in the behavioral results, but a trend toward overestimation of intervals ≤11.9s and underestimation of intervals ≥14.1s in the OFF condition (p<0.088). During the reproduction phase, higher activation in the precuneus was found in the ON condition (p<0.05 corrected). Time course was plotted separately for long (≥14.1s) and short (≤11.9s) intervals. Results showed that there was a significant difference only in long intervals, when activity gradually decreased in the OFF, but remained stable in the ON condition. This difference in precuneus activation was not found during random button presses in a control task.
Our results show that differences in precuneus activation during retrieval of a remembered duration may underlie some aspects of time perception deficit in PD patients. We suggest that DA medication may allow compensatory activation in the precuneus, which results in a more accurate retrieval of remembered interval duration.
PMCID: PMC3253091  PMID: 22238630
11.  Basal Ganglia MR Relaxometry in Obsessive-Compulsive Disorder: T2 Depends Upon Age of Symptom Onset 
Brain imaging and behavior  2009;4(1):35-45.
Dysfunction in circuits linking frontal cortex and basal ganglia (BG) is strongly implicated in obsessive-compulsive disorder (OCD). On MRI studies, neuropsychiatric disorders with known BG pathology have abnormally short T2 relaxation values (a putative biomarker of elevated iron) in this region. We asked if BG T2 values are abnormal in OCD. We measured volume and T2 and T1 relaxation rates in BG of 32 adults with OCD and 33 matched controls. There were no group differences in volume or T1 values in caudate, putamen, or globus pallidus (GP). The OCD group had lower T2 values (suggesting higher iron content) in the right GP, with a trend in the same direction for the left GP. This effect was driven by patients whose OCD symptoms began from around adolescence to early adulthood. The results suggest a possible relationship between age of OCD onset and iron deposition in the basal ganglia.
PMCID: PMC3018344  PMID: 20503112
Obsessive-compulsive disorder; Basal ganglia; Age of onset; Iron; Magnetic Resonance Imaging
12.  Chemotherapeutic treatment efficacy and sensitivity are increased by adjuvant alternating electric fields (TTFields) 
The present study explores the efficacy and toxicity of combining a new, non-toxic, cancer treatment modality, termed Tumor Treating Fields (TTFields), with chemotherapeutic treatment in-vitro, in-vivo and in a pilot clinical trial.
Cell proliferation in culture was studied in human breast carcinoma (MDA-MB-231) and human glioma (U-118) cell lines, exposed to TTFields, paclitaxel, doxorubicin, cyclophosphamide and dacarbazine (DTIC) separately and in combinations. In addition, we studied the effects of combining chemotherapy with TTFields in an animal tumor model and in a pilot clinical trial in recurrent and newly diagnosed GBM patients.
The efficacy of TTFields-chemotherapy combination in-vitro was found to be additive with a tendency towards synergism for all drugs and cell lines tested (combination index ≤ 1). The sensitivity to chemotherapeutic treatment was increased by 1–3 orders of magnitude by adjuvant TTFields therapy (dose reduction indexes 23 – 1316). Similar findings were seen in an animal tumor model. Finally, 20 GBM patients were treated with TTFields for a median duration of 1 year. No TTFields related systemic toxicity was observed in any of these patients, nor was an increase in Temozolomide toxicity seen in patients receiving combined treatment. In newly diagnosed GBM patients, combining TTFields with Temozolomide treatment led to a progression free survival of 155 weeks and overall survival of 39+ months.
These results indicate that combining chemotherapeutic cancer treatment with TTFields may increase chemotherapeutic efficacy and sensitivity without increasing treatment related toxicity.
PMCID: PMC2647898  PMID: 19133110

Results 1-12 (12)