Association of Tumor Treating Fields (TTFields) therapy with survival in newly diagnosed glioblastoma: a systematic review and meta-analysis.

PURPOSE: Tumor Treating Fields (TTFields) therapy, an electric field-based cancer treatment, became FDA-approved for patients with newly diagnosed glioblastoma (GBM) in 2015 based on the randomized controlled EF-14 study. Subsequent approvals worldwide and increased adoption over time have raised the question of whether a consistent survival benefit has been observed in the real-world setting, and whether device usage has played a role. METHODS: We conducted a literature search to identify clinical studies evaluating overall survival (OS) in TTFields-treated patients. Comparative and single-cohort studies were analyzed. Survival curves were pooled using a distribution-free random-effects method. RESULTS: Among nine studies, seven (N = 1430 patients) compared the addition of TTFields therapy to standard of care (SOC) chemoradiotherapy versus SOC alone and were included in a pooled analysis for OS. Meta-analysis of comparative studies indicated a significant improvement in OS for patients receiving TTFields and SOC versus SOC alone (HR: 0.63; 95% CI 0.53-0.75; p < 0.001). Among real-world post-approval studies, the pooled median OS was 22.6 months (95% CI 17.6-41.2) for TTFields-treated patients, and 17.4 months (95% CI 14.4-21.6) for those not receiving TTFields. Rates of gross total resection were generally higher in the real-world setting, irrespective of TTFields use. Furthermore, for patients included in studies reporting data on device usage (N = 1015), an average usage rate of ≥ 75% was consistently associated with prolonged survival (p < 0.001). CONCLUSIONS: Meta-analysis of comparative TTFields studies suggests survival may be improved with the addition of TTFields to SOC for patients with newly diagnosed GBM.

Quantification of artifacts during cardiac magnetic resonance in patients with leadless Micra pacemakers.

INTRODUCTION: When cardiac magnetic resonance (MR) is performed after previous leadless transcatheter pacemaker implantation, an image distortion has to be expected in the heart region and evaluation of myocardial tissue can be affected. In this clinical prospective study, we aim to assess the extent and impact of this artifact on individual ventricular segments and compare it to conventional pacing devices. METHODS: Total of 20 patients with leadless pacemaker placed in the right ventricle underwent cardiac MR imaging in a 1.5 Tesla scanner. A multiplanar segmentation was used to demarcate the left and right ventricular myocardium as well as the pacemaker-caused image artifact in systolic and diastolic time frames. Artifact size and its relative influence on myocardial segments were quantitatively assessed and expressed in AHA-17 model. RESULTS: Implanted leadless pacemaker caused an image artifact with a volume of 48 ± 5 ml. Most distorted were the apical septal (53 ± 23%), apical inferior (30 ± 18%), and midventricular inferoseptal (30 ± 20%) segments. The artifact intersection with basal and lateral segments was none or negligible (up to 2%). The portion of left ventricular (LV) myocardium affected by the artifact was significantly higher in systole (8 ± 4%) compared to diastole (10 ± 3%; p < .001). CONCLUSION: Implantation of leadless pacemaker represents no obstacle for cardiac MR imaging but causes an image artifact located mostly in septal, inferoseptal, and anteroseptal segments of apical and midventricular LV myocardium. With the exception of the apex, diastolic timing reduces the image distortion of all segments and improves global ventricular assessment.

Dose-Lowering in Contrast-Enhanced MRI of the Central Nervous System: A Retrospective, Parallel-Group Comparison Using Gadobenate Dimeglumine.

BACKGROUND: Concerns over gadolinium (Gd) retention encourage the use of lower Gd doses. However, lower Gd doses may compromise imaging performance. Higher relaxivity gadobenate may be suited to reduced dose protocols. PURPOSE: To compare 0.05 mmol/kg and 0.1 mmol/kg gadobenate in patients undergoing enhanced MRI of the central nervous system (CNS). STUDY TYPE: Retrospective, multicenter. POPULATION: Three hundred and fifty-two patients receiving 0.05 (n = 181) or 0.1 (n = 171) mmol/kg gadobenate. FIELD STRENGTH/SEQUENCES: 1.5 T and 3.0 T/precontrast and postcontrast T1-weighted spin echo/fast spin echo (SE/FSE) and/or gradient echo/fast field echo (GRE/FFE); precontrast T2-weighted FSE and T2-FLAIR. ASSESSMENT: Images of patients with extra-axial lesions at 1.5 T or any CNS lesion at 3.0 T were reviewed by three blinded, independent neuroradiologists for qualitative (lesion border delineation, internal morphology visualization, contrast enhancement; scores from 1 = poor to 4 = excellent) and quantitative (lesion-to-brain ratio [LBR], contrast-to-noise ratio [CNR]; SI measurements at regions-of-interest on lesion and normal parenchyma) enhancement measures. Noninferiority of 0.05 mmol/kg gadobenate was determined for each qualitative endpoint if the lower limit of the 95% confidence interval (CI) for the difference in precontrast + postcontrast means was above a noninferiority margin of -0.4. STATISTICAL TESTS: Student's t-test for comparison of mean qualitative endpoint scores, Wilcoxon signed rank test for comparison of LBR and CNR values; Wilcoxon rank sum test for comparison of SI changes. Tests were significant for P < 0.05. RESULTS: The mean change from precontrast to precontrast + postcontrast was significant for all endpoints. Readers 1, 2, and 3 evaluated 304, 225, and 249 lesions for 0.05 mmol/kg gadobenate, and 382, 309, and 298 lesions for 0.1 mmol/kg gadobenate. The lower limit of the 95% CI was above -0.4 for all comparisons. Significantly, higher LBR and CNR was observed with the higher dose. DATA CONCLUSION: 0.05 mmol/kg gadobenate was noninferior to 0.1 mmol/kg gadobenate for lesion visualization. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

Gamma Knife Radiosurgery of Distal Aneurysm: A Case Series.

A series of 3 patients (35-60 years old) with bleeding distal aneurysm not associated with AVM who underwent radiosurgery by gamma knife are reported. One isocentre centralized over the aneurysm was used; peripheral dose 24-28.8 Gy was applied. Control angiography 20-36 months after gamma knife surgery (GKS) demonstrated obliteration of both the aneurysm and the feeding artery, without deterioration of the neurological symptoms. Our case series implies that GKS might serve as a safe mini-invasive technique in the treatment of selected distal aneurysms.

Safety and diagnostic efficacy of gadoteridol for magnetic resonance imaging of the brain and spine in children 2 years of age and younger.

BACKGROUND: Neonates and young children require efficacious magnetic resonance imaging (MRI) examinations but are potentially more susceptible to the short- and long-term adverse effects of gadolinium-based contrast agents due to the immaturity of their body functions. OBJECTIVE: To evaluate the acute safety and diagnostic efficacy of gadoteridol (ProHance) for contrast-enhanced MRI of the central nervous system (CNS) in children ≤2 years of age. MATERIALS AND METHODS: One hundred twenty-five children ≤2 years old (including 57 children <6 months old) who underwent contrast-enhanced MRI of the CNS with gadoteridol at 0.1 mmol/kg body weight were retrospectively enrolled at five imaging centers. Safety data were assessed for acute/subacute adverse events in the 48 h following gadoteridol administration and, when available, vital signs, electrocardiogram (ECG) and clinical laboratory values obtained from blood samples taken from 48 h before until 48 h following the MRI exam. The efficacy of gadoteridol-enhanced MRI compared to unenhanced MRI for disease diagnosis was evaluated prospectively by three blinded, unaffiliated readers. RESULTS: Thirteen changes of laboratory values (11 mild, 1 moderate, 1 unspecified) were reported as adverse events in 7 (5.6%) patients. A relationship to gadoteridol was deemed possible though doubtful for two of these adverse events in two patients (1.6%). There were no clinical adverse events, no serious adverse events and no clinically meaningful changes in vital signs or ECG recordings. Accurate differentiation of tumor from non-neoplastic disease, and exact matching of specific MRI-determined diagnoses with on-site final diagnoses, was achieved in significantly more patients by each reader following the evaluation of combined pre- and post-contrast images compared to pre-contrast images alone (84.6-88.0% vs. 70.9-76.9%; P≤0.006 and 67.5-79.5% vs. 47.0-66.7%; P≤0.011, respectively). CONCLUSION: Gadoteridol at 0.1 mmol/kg body weight is safe, well tolerated and effective for contrast-enhanced MRI of the CNS in children ≤2 years of age.

Whole brain apparent diffusion coefficient measurements correlate with survival in glioblastoma patients.

INTRODUCTION: Glioblastoma (GBM) is the most common malignant primary brain tumor, and methods to improve the early detection of disease progression and evaluate treatment response are highly desirable. We therefore explored changes in whole-brain apparent diffusion coefficient (ADC) values with respect to survival (progression-free [PFS], overall [OS]) in a cohort of GBM patients followed at regular intervals until disease progression. METHODS: A total of 43 subjects met inclusion criteria and were analyzed retrospectively. Histogram data were extracted from standardized whole-brain ADC maps including skewness, kurtosis, entropy, median, mode, 15th percentile (p15) and 85th percentile (p85) values, and linear regression slopes (metrics versus time) were fitted. Regression slope directionality (positive/negative) was subjected to univariate Cox regression. The final model was determined by aLASSO on metrics above threshold. RESULTS: Skewness, kurtosis, median, p15 and p85 were all below threshold for both PFS and OS and were analyzed further. Median regression slope directionality best modeled PFS (p = 0.001; HR 3.3; 95% CI 1.6-6.7), while p85 was selected for OS (p = 0.002; HR 0.29; 95% CI 0.13-0.64). CONCLUSIONS: Our data show tantalizing potential in the use of whole-brain ADC measurements in the follow up of GBM patients, specifically serial median ADC values which correlated with PFS, and serial p85 values which correlated with OS. Whole-brain ADC measurements are fast and easy to perform, and free of ROI-placement bias.

Modulatory Effects of Levodopa on Cerebellar Connectivity in Parkinson's Disease.

Levodopa has been the mainstay of symptomatic therapy for Parkinson's disease (PD) for the last five decades. However, it is associated with the development of motor fluctuations and dyskinesia, in particular after several years of treatment. The aim of this study was to shed light on the acute brain functional reorganization in response to a single levodopa dose. Functional magnetic resonance imaging (fMRI) was performed after an overnight withdrawal of dopaminergic treatment and 1 h after a single dose of 250 mg levodopa in a group of 24 PD patients. Eigenvector centrality was calculated in both treatment states using resting-state fMRI. This offers a new data-driven and parameter-free approach, similar to Google's PageRank algorithm, revealing brain connectivity alterations due to the effect of levodopa treatment. In all PD patients, levodopa treatment led to an improvement of clinical symptoms as measured with the Unified Parkinson's Disease Rating Scale motor score (UPDRS-III). This therapeutic effect was accompanied with a major connectivity increase between cerebellar brain regions and subcortical areas of the motor system such as the thalamus, putamen, globus pallidus, and brainstem. The degree of interconnectedness of cerebellar regions correlated with the improvement of clinical symptoms due to the administration of levodopa. We observed significant functional cerebellar connectivity reorganization immediately after a single levodopa dose in PD patients. Enhanced general connectivity (eigenvector centrality) was associated with better motor performance as assessed by UPDRS-III score. This underlines the importance of considering cerebellar networks as therapeutic targets in PD.

Role of gamma knife radiosurgery in the treatment of prolactinomas.

PURPOSE: Stereotactic radiosurgery is one of the treatment options for prolactinomas, the most commonly used being Gamma Knife Radiosurgery (GKRS). GKRS is indicated mainly in the treatment of dopamine agonist (DA)-resistant prolactinomas. In our study, we report on our experience in treating prolactinoma patients by GKRS. METHODS: Twenty-eight patients were followed-up after GKRS for 26-195 months (median 140 months). Prior to GKRS, patients were treated with DAs and 9 of them (32.1%) underwent previous neurosurgery. Cavernous sinus invasion was present in 16 (57.1%) patients. Indications for GKRS were (i) resistance to DA treatment (17 patients), (ii) drug intolerance (5 patients), or (iii) attempts to reduce the dosage and/or shorten the length of DA treatment (6 patients). RESULTS: After GKRS, normoprolactinaemia was achieved in 82.1% of patients, out of which hormonal remission (normoprolactinaemia after discontinuation of DAs) was achieved in 13 (46.4%), and hormonal control (normoprolactinaemia while taking DAs) in 10 (35.7%) patients. GKRS arrested adenoma growth or decreased adenoma size in all cases. Two patients (8.3%) developed hypopituitarism after GKRS. Prolactinoma cystic transformation with expansive behaviour, manifested by bilateral hemianopsia, was observed in one patient. CONCLUSIONS: GKRS represents an effective treatment option, particularly for DA-resistant prolactinomas. Normoprolactinaemia was achieved in the majority of patients, either after discontinuation of, or while continuing to take, DAs. Tumour growth was arrested in all cases. The risk of the development of hypopituitarism can be limited if the safe dose to the pituitary and infundibulum is maintained.

Vertebroplasty and epiduroscopy as seen by interventional radiologist.

Two minimally-invasive techniques in the spinal region are introduced: vertebroplasty and epiduroscopy. Vertebroplasty is mostly used in the treatment of osteoporotic vertebral body fractures, as well as in the palliative treatment of spinal metastases or symptomatic hemangiomas. It is usually performed under fluoroscopic, and often also CT control under analgesic sedation. If correctly indicated an analgesic effect occurs in roughly 90 % of patients. Epiduroscopy is a new technique, which is promising especially in patients with failed back surgery syndrome; patients with clinically-symptomatic fibrous adhesions, generally after repeated surgery. If correctly indicated a positive effect occurs in roughly one third to one half of patients.

Magnetic resonance imaging in patients with a subcutaneous implantable cardioverter-defibrillator.

AIMS: 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. CONCLUSION: 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.

Radiosurgery for Large Arteriovenous Malformations as a Single-Session or Staged Treatment.

BACKGROUND/OBJECTIVES: The treatment of large arteriovenous malformations (AVMs) presents a challenge and the effectiveness of radiosurgery decreases with increasing treatment volume. Here, we analyzed and compared single-session treatment for AVMs >15 cm3 with staged treatment, when the volume of a large AVM was divided into 2 or more compartments, which were subsequently treated at intervals of a few months. In the event that complete obliteration was not achieved within 3 years, repeat radiosurgery was considered. METHODS/RESULTS: Between 1993 and 2011, gamma-knife radiosurgery was performed on 50 patients with large AVMs. A total of 27 of them, with volumes ranging from 15.1 to 27 cm3 (median = 17.8), were treated in a single session, with a marginal dose ranging from 10 to 17 Gy (median = 15). Complete obliteration was achieved in 7 (26%) of these; in 14 patients the treatment was repeated after a median of 38 months. The volume of AVMs subjected to repeat treatment regressed and ranged from 6.76 to 16.4 cm3 (median = 7.7), with the marginal dose ranging from 13 to 18 Gy (median = 17); 10 patients later achieved complete obliteration at a median of 79 months after the initial treatment. Overall, 63% of patients achieved complete obliteration of AVM after treatment. Rebleeding in a latent period was recorded in 3 patients (11%) and symptomatic collateral edema in 2 (7%); 23 patients were treated using the staged method, with the interval between staged treatments usually being 6 months. Their overall AVM volume ranged from 13.2 to 46.6 cm3 (median = 23.3), the volume for a single stage ranged from 4.5 to 31.3 cm3 (median 11.7), and the marginal dose ranged from 10 to 18 Gy (median = 17). Complete obliteration was achieved in 4 (17%) of them, in 8 patients the treatment was repeated at a median of 53 months after the first treatment, and a third retreatment was performed on 2 patients 98 and 102 months, respectively, after the first treatment. The volume for repeated treatment of AVMs ranged from 0.81 to 7.7 cm3 (median = 3.3), with the marginal dose ranging from 14 to 20 Gy (median 17.5). Of all the retreated patients, 5 AVMs subsequently achieved complete obliteration. Overall, 9 patients (39%) were totally cured. Rebleeding in a latent period was observed in 1 of these patients (4.3%) and symptomatic edema in another 1 (4.3%). CONCLUSIONS: Radiosurgery of large AVMs is a valuable treatment either as a single-session or staged treatment, with a reasonable chance of cure and a low risk of complications.

MRI contrast agents and retention in the brain: review of contemporary knowledge and recommendations to the future.

Gadolinium-based contrast agents (GBCA) were introduced with high expectations for favorable efficacy, low nephrotoxicity, and minimal allergic-like reactions. Nephrogenic systemic fibrosis and proven gadolinium retention in the body including the brain has led to the restriction of linear GBCAs and a more prudent approach regarding GBCA indication and dosing. In this review, we present the chemical, physical, and clinical aspects of this topic and aim to provide an equanimous and comprehensive summary of contemporary knowledge with a perspective of the future. In the first part of the review, we present various elements and compounds that may serve as MRI contrast agents. Several GBCAs are further discussed with consideration of their relaxivity, chelate structure, and stability. Gadolinium retention in the brain is explored including correlation with the presence of metalloprotein ferritin in the same regions where visible hyperintensity on unenhanced T1-weighted imaging occurs. Proven interaction between ferritin and gadolinium released from GBCAs is introduced and discussed, as well as the interaction of other elements with ferritin; and manganese in patients with impaired liver function or calcium in Fahr disease. We further present the concept that only high-molecular-weight forms of gadolinium can likely visibly change signal intensity on unenhanced T1-weighted imaging. Clinical data are also presented with respect to potential neurological manifestations originating from the deep-brain nuclei. Finally, new contrast agents with relatively high relaxivity and stability are introduced. CRITICAL RELEVANCE STATEMENT: GBCA may accumulate in the brain, especially in ferritin-rich areas; however, no adverse neurological manifestations have been detected in relation to gadolinium retention. KEY POINTS: Gadolinium currently serves as the basis for MRI contrast agents used clinically. No adverse neurological manifestations have been detected in relation to gadolinium retention. Future contrast agents must advance chelate stability and relativity, facilitating lower doses.

Comparison between postcontrast thin-slice T1-weighted 2D spin echo and 3D T1-weighted SPACE sequences in the detection of brain metastases at 1.5 and 3 T.

OBJECTIVES: Accurate detection of metastatic brain lesions (MBL) is critical due to advances in radiosurgery. We compared the results of three readers in detecting MBL using T1-weighted 2D spin echo (SE) and sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) sequences with whole-brain coverage at both 1.5 T and 3 T. METHODS: Fifty-six patients evaluated for MBL were included and underwent a standard protocol (1.5 T, n = 37; 3 T, n = 19), including postcontrast T1-weighted SE and SPACE. The rating was performed by three raters in two sessions > six weeks apart. The true number of MBL was determined using all available imaging including follow-up. Intraclass correlations for intra-rater and inter-rater agreement were calculated. Signal intensity ratios (SIR; enhancing lesion, white matter) were determined on a subset of 46 MBL > 4 mm. A paired t-test was used to evaluate postcontrast sequence order and SIR. Reader accuracy was evaluated by the coefficient of determination. RESULTS: A total of 135 MBL were identified (mean/subject 2.41, SD 6.4). The intra-rater agreement was excellent for all 3 raters (ICC = 0.97-0.992), as was the inter-rater agreement (ICC = 0.995 SE, 0.99 SPACE). Subjective qualitative ratings were lower for SE images; however, signal intensity ratios were higher in SE sequences. Accuracy was high in all readers for both SE (R2 0.95-0.96) and SPACE (R2 0.91-0.96) sequences. CONCLUSIONS: Although SE sequences are superior to gradient echo sequences in the detection of small MBL, they have long acquisition times and frequent artifacts. We show that T1-weighted SPACE is not inferior to standard thin-slice SE sequences in the detection of MBL at both imaging fields. CRITICAL RELEVANCE STATEMENT: Our results show the suitability of 3D T1-weighted turbo spin echo (TSE) sequences (SPACE, CUBE, VISTA) in the detection of brain metastases at both 1.5 T and 3 T. KEY POINTS: • Accurate detection of brain metastases is critical due to advances in radiosurgery. • T1-weighted SE sequences are superior to gradient echo in detecting small metastases. • T1-weighted 3D-TSE sequences may achieve high resolution and relative insensitivity to artifacts. • T1-weighted 3D-TSE sequences have been recommended in imaging brain metastases at 3 T. • We found T1-weighted 3D-TSE equivalent to thin-slice SE at 1.5 T and 3 T.

Chasing shadows: what determines DTI metrics in gray matter regions? An in vitro and in vivo study.

PURPOSE: To characterize the relationship between superparamagnetic ferritin-bound iron and diffusion tensor scalars in vitro, and validate the results in vivo. MATERIALS AND METHODS: The in vitro model consisted of a series of 40-mL 1.1% agarose gels doped with ferritin covering and exceeding those concentrations normally found within healthy human gray matter. Additionally, regions of interest were placed in the caudate, putamen, and globus pallidus of 29 healthy volunteer subjects 19-80 years of age. Carr-Purcell-Meiboom-Gill sequence (CPMG) and diffusion tensor imaging (DTI) data were collected at 1.5 Tesla (T) and 3T in vitro, and at 1.5T in vivo. RESULTS: In vitro, linear relationships were observed between ferritin-bound iron concentration, R2 (1/T2 ) and 1/SNR. Eigenvalue repulsion with increasing R2 (decreasing SNR) was reflected in an artifactual increase of fractional anisotropy. In vivo, similar relationships were observed, with mean diffusivity also decreasing linearly with increasing R2 . Lambda 3 showed the strongest correlation with R2 both in vitro and in vivo. CONCLUSION: The observation that DTI metrics correlate with ferritin-bound iron is an important consideration in the design and interpretation of studies exploring the diffusion characteristics of gray matter regions, especially in studies focused on adolescence as well as diseases associated with altered brain-iron load such as pantothenate kinase-associated neurodegeneration, Huntington disease and multiple system atrophy.

Gamma knife radiosurgery of brain cavernomas.

PURPOSE: Radiosurgery of cavernomas should prevent rebleeding, growth of the lesion, and deterioration of clinical symptoms. However, there is no direct diagnostic tool to verify the endpoints of treatment. At present, the positive effects of radiosurgery are identified by clinical observation and analysis of imaging changes on magnetic resonance imaging during a sufficiently long follow-up period. METHODS: Between 1992 and 2000, a total of 112 patients with brain cavernomas were treated with Gamma Knife radiosurgery at our center. In all, 59 patients experienced bleeding before radiosurgery; the remainder did not. The median age of patients was 42 years, the median volume of the cavernomas was 0.9 cm(3), and the median applied marginal dose was 16 Gy. RESULTS: After a 2-year latent interval after treatment (median follow-up 84 months), the risk of bleeding in the group of patients with bleeding before radiosurgery had decreased from 3.7 % to 0.2 %. For the patients without bleeding before radiosurgery, the annual risk of bleeding was 0.8 %. The cavernoma size decreased in 53.0 % of cases and increased in 6.4 %. Epilepsy, if present before the treatment, was alleviated in 45 % of cases. The risks of temporary or permanent morbidity caused by radiosurgery were 14.6 % and 0.9 %, respectively. CONCLUSION: Radiosurgery of cavernomas was associated with a low risk of permanent morbidity. The risk of rebleeding after the 2-year latent interval after radiosurgery had decreased. Treatment of cavernomas with no history of bleeding was halted at our center.

Improving fMRI in Parkinson's disease by accounting for brain region-specific activity patterns.

In functional magnetic imaging (fMRI) in Parkinson's disease (PD), a paradigm consisting of blocks of finger tapping and rest along with a corresponding general linear model (GLM) is often used to assess motor activity. However, this method has three limitations: (i) Due to the strong magnetic field and the confined environment of the cylindrical bore, it is troublesome to accurately monitor motor output and, therefore, variability in the performed movement is typically ignored. (ii) Given the loss of dopaminergic neurons and ongoing compensatory brain mechanisms, motor control is abnormal in PD. Therefore, modeling of patients' tapping with a constant amplitude (using a boxcar function) and the expected Parkinsonian motor output are prone to mismatch. (iii) The motor loop involves structures with distinct hemodynamic responses, for which only one type of modeling (e.g., modeling the whole block of finger tapping) may not suffice to capture these structure's temporal activation. The first two limitations call for considering results from online recordings of the real motor output that may lead to significant sensitivity improvements. This was shown in previous work using a non-magnetic glove to capture details of the patients' finger movements in a so-called kinematic approach. For the third limitation, modeling motion initiation instead of the whole tapping block has been suggested to account for different temporal activation signatures of the motor loop's structures. In the present study we propose improvements to the GLM as a tool to study motor disorders. For this, we test the robustness of the kinematic approach in an expanded cohort (n = 31), apply more conservative statistics than in previous work, and evaluate the benefits of an event-related model function. Our findings suggest that the integration of the kinematic approach offers a general improvement in detecting activations in subcortical structures, such as the basal ganglia. Additionally, modeling motion initiation using an event-related design yielded superior performance in capturing medication-related effects in the putamen. Our results may guide adaptations in analysis strategies for functional motor studies related to PD and also in more general applications.

Quantitative MR imaging and spectroscopy of brain tumours: a step forward?

OBJECTIVES: A prospective quantitative MR study of brain tumours was performed to show the potential of combining different MR techniques to distinguish various disease processes in routine clinical practice. METHODS: Twenty-three patients with various intracranial tumours before treatment (diagnosis confirmed by a biopsy) and 59 healthy subjects were examined on a 3-T system by conventional MR imaging, 1H spectroscopic imaging, diffusion tensor imaging and T2 relaxometry. Metabolic concentrations and their ratios, T2 relaxation times and mean diffusivities were calculated and correlated on a pixel-by-pixel basis and compared to control data. RESULTS: Different tumour types and different localisations revealed specific patterns of correlations between metabolic concentrations and mean diffusivity or T2 relaxation times. The patterns distinguish given tissue states in the examined area: healthy tissue, tissue infiltrated by tumour, active tumour, oedema infiltrated by tumour, oedema, etc. This method is able to describe the complexity of a highly heterogeneous tissue in the tumour and its vicinity, and determines crucial parameters for tissue differentiation. CONCLUSIONS: A combination of different MR parameters on a pixel-by-pixel basis in individual patients enables better identification of the tumour type, direction of proliferation and assessment of the tumour extension. KEY POINTS : • Magnetic resonance offers many different methods of examining the brain. • A combination of quantitative MR parameters helps distinguish different brain lesions • Different tumour types revealed specific correlation patterns amongst different MR parameters • The correlation patterns reflect highly heterogeneous complex tissue within tumours.

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.