Spyros Kollias

SENSE-DTI at 3 T

While holding vast potential, diffusion tensor imaging (DTI) with single‐excitation protocols still faces serious challenges. Limited spatial resolution, susceptibility to magnetic field inhomogeneity, and low signal‐to‐noise ratio (SNR) may be considered the most prominent limitations. It is demonstrated that all of these shortcomings can be effectively mitigated by the transition to parallel imaging technology and high magnetic field strength. Using the sensitivity encoding (SENSE) technique at 3 T, brain DTI was performed in nine healthy volunteers. Despite enhanced field inhomogeneity, parallel acquisition permitted both controlling geometric distortions and enhancing spatial resolution up to 0.8 mm in‐plane. Heightened SNR requirements were met in part by high base sensitivity at 3 T. A further significant increase in SNR efficiency was accomplished by SENSE acquisition, exploiting enhanced encoding speed for echo time reduction. Based on the resulting image data, high‐resolution tensor mapping is demonstrated. Magn Reson Med 51:230–236, 2004.

PRESTO-SENSE: An ultrafast whole-brain fMRI technique

A new ultrafast MR imaging method is proposed and tested, which enables whole‐brain fMRI with a true temporal resolution of 1 sec. The method combines a 3D PRESTO pulse sequence with the concept of sensitivity‐encoding with multiple receiver coils (SENSE). The so‐called PRESTO‐SENSE technique is demonstrated on a set of functional block‐type motor and visual experiments and compared with conventional functional imaging techniques, such as PRESTO and EPI. Comparable image quality and activation areas are found with all sequences. The noise characteristics of the proposed method are analyzed in detail and their implications for ultrafast fMRI studies are discussed. Magn Reson Med 43:779–786, 2000.

Noninvasive measurement of regional cerebral blood flow and regional cerebral blood volume by near-infrared spectroscopy and indocyanine green dye dilution.

To find a suitable method for measuring regional cerebral blood flow (rCBF) rapidly at the bedside is still a matter of investigation. The purpose here was to develop a noninvasive method for bedside rCBF measurement and to validate it with a standard method such as perfusion-weighted magnetic resonance imaging (MRI). In 11 healthy volunteers 44 measurements with near-infrared spectroscopy (NIRS) and perfusion-weighted MRI without and with a mean continuous positive airway pressure (CPAP) of 10 mbar were carried out. Four (NIRS) optodes were placed bilaterally on the forehead and 25 mg indocyanine green (ICG) was injected. New algorithms were developed to calculate rCBFNIRS and rCBVNIRS. In 6 volunteers data analysis was successful. No complications associated with the method were observed. During CPAP breathing rCBFNIRS decreased from 18.5 + 6.9 16.1 + 6.2 ml/100 g/min (P = 0.034). Mean values for rCBFMRI decreased from 256 +/- 90 to 216 +/- 62 ml/100 g/min (P = 0.012). Bland and Altman plots showed that the differences did not vary in any systematic way over the range of rCBF or rCBV values assessed and 100% of differences were within the interval mean +/- 2 SD of differences. Limits of agreement (mean +/- 2 SD) were +/- 76.4 ml/100 g/min for rCBF and +/- 15.6 ml/100 g for rCBV. The NIRS ICG dye dilution technique is a promising method for serial noninvasive bedside CBF measurements. The preliminary data indicate that measurements are in agreement with values obtained by perfusion-weighted MRI.

An fMRI study of the role of suprapontine brain structures in the voluntary voiding control induced by pelvic floor contraction.

We have learned that micturition is comprised of two basic phases: storage and emptying; during bladder emptying, the pontine and periaqueductal gray (PAG) micturition center ensures coordinated inhibition of striated sphincter and pelvic floor muscles and relaxation of the internal urethral sphincter while the detrusor muscle contracts. Due to several disorders of the brain and spinal cord, the achieved voluntary control of bladder function can be impaired, and involuntary mechanisms of bladder activation again become evident. However, little has been discovered so far how higher brain centers strictly regulate the intricate process of micturition. The present functional magnetic resonance imaging (fMRI) study attempted to identify brain areas involved in such voluntary control of the micturition reflex by performing functional magnetic resonance imaging during a block design experiment in 12 healthy subjects. The protocol consisted of alternating periods of rest and pelvic muscle contraction during empty-bladder condition (EBC) and full-bladder condition (FBC). Repeated pelvic floor muscle contractions were performed during full bladder to induce a stronger contrast of bladder sensation, desire to void and inhibition of the micturition reflex triggering, since the subjects were asked not to urinate. Empty-bladder conditions were applied as control groups. Activation maps calculated by contrast of subtracting the two different conditions were purposed to disclose these brain areas that are involved during the inhibition of the micturition reflex, in which contrast, the SMA, bilateral putamen, right parietal cortex, right limbic system, and right cerebellum were found activated. The combined activation of basal ganglia, parietal cortex, limbic system, and cerebellum might support the assumption that a complex visceral sensory-motor program is involved during the inhibitory control of the micturition reflex.

Preservation of motor programs in paraplegics as demonstrated by attempted and imagined foot movements

Execution and imagination of movement activate distinct neural circuits, partially overlapping in premotor and parietal areas, basal ganglia and cerebellum. Can long-term deafferented/deefferented patients still differentiate attempted from imagined movements? The attempted execution and motor imagery network of foot movements have been investigated in nine chronic complete spinal cord-injured (SCI) patients using fMRI. Thorough behavioral assessment showed that these patients were able to differentiate between attempted execution and motor imagery. Supporting the outcome of the behavioral assessment, fMRI disclosed specific patterns of activation for movement attempt and for motor imagery. Compared with motor execution data of healthy controls, movement attempt in SCI patients revealed reduced primary motor cortex activation at the group level, although activation was found in all single subjects with a high variability. Further comparisons with healthy subjects revealed that during attempt and motor imagery, SCI patients show enhanced activation and recruitment of additional regions in the parietal lobe and cerebellum that are important in sensorimotor integration. These findings reflect central plastic changes due to altered input and output and suggest that SCI patients may require additional cognitive resources to perform these tasks that may be one and the same phenomenon, or two versions of the same phenomenon, with quantitative differences between the two. Nevertheless, the retained integrity of movement attempt and motor imagery networks in SCI patients demonstrates that chronic paraplegics can still dispose of the full motor programs for foot movements and that therefore, attempted and imagined movements should be integrated in rehabilitative strategies.

MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial.

Purpose: Rechallenge with temozolomide (TMZ) at first progression of glioblastoma after temozolomide chemoradiotherapy (TMZ/RT→TMZ) has been studied in retrospective and single-arm prospective studies, applying temozolomide continuously or using 7/14 or 21/28 days schedules. The DIRECTOR trial sought to show superiority of the 7/14 regimen. Experimental Design: Patients with glioblastoma at first progression after TMZ/RT→TMZ and at least two maintenance temozolomide cycles were randomized to Arm A [one week on (120 mg/m2 per day)/one week off] or Arm B [3 weeks on (80 mg/m2 per day)/one week off]. The primary endpoint was median time-to-treatment failure (TTF) defined as progression, premature temozolomide discontinuation for toxicity, or death from any cause. O6-methylguanine DNA methyltransferase (MGMT) promoter methylation was prospectively assessed by methylation-specific PCR. Results: Because of withdrawal of support, the trial was prematurely closed to accrual after 105 patients. There was a similar outcome in both arms for median TTF [A: 1.8 months; 95% confidence intervals (CI), 1.8–3.2 vs. B: 2.0 months; 95% CI, 1.8–3.5] and overall survival [A: 9.8 months (95% CI, 6.7–13.0) vs. B: 10.6 months (95% CI, 8.1–11.6)]. Median TTF in patients with MGMT-methylated tumors was 3.2 months (95% CI, 1.8–7.4) versus 1.8 months (95% CI, 1.8–2) in MGMT-unmethylated glioblastoma. Progression-free survival rates at 6 months (PFS-6) were 39.7% with versus 6.9% without MGMT promoter methylation. Conclusions: Temozolomide rechallenge is a treatment option for MGMT promoter-methylated recurrent glioblastoma. Alternative strategies need to be considered for patients with progressive glioblastoma without MGMT promoter methylation. Clin Cancer Res; 21(9); 2057–64. ©2015 AACR.

Neural Correlates for the Acquisition of Natural Language Syntax

Some types of simple and logically possible syntactic rule never occur in human language grammars, leading to a distinction between grammatical and nongrammatical syntactic rules. Comparison of the neuroanatomical correlates underlying the acquisition of grammatical and nongrammatical rules can provide relevant evidence on the neural processes dedicated to language acquisition in a given developmental stage. Until present no direct evidence on the neural mechanisms subserving language acquisition at any developmental stage has been supplied. We used fMRI in investigating the acquisition of grammatical and nongrammatical rules in the specified sense in 14 healthy adults. Grammatical rules compared with nongrammatical rules specifically activated a left hemispheric network including Brocas area, as shown by direct comparisons between the two rule types. The selective role of Brocas area was further confirmed by time x condition interactions and by proficiency effects, in that higher proficiency in grammatical rule usage, but not in usage of nongrammatical rules, led to higher levels of activation in this area. These findings provide evidence for the neural mechanisms underlying language acquisition in adults.

Mcleod syndrome: A novel mutation, predominant psychiatric manifestations, and distinct striatal imaging findings

The McLeod syndrome is an X‐linked disorder caused by mutations of the XK gene encoding the XK protein. The syndrome is characterized by absent Kx erythrocyte antigen, weak expression of Kell blood group system antigens, and acanthocytosis. In some allelic variants, elevated creatine kinase, myopathy, neurogenic muscle atrophy, and progressive chorea are found. We describe a family with a novel point mutation in the XK gene consisting of a C to T base transition at nucleotide position 977, introducing a stop codon. Among seven affected males, five manifested with psychiatric disorders such as depression, bipolar disorder, or personality disorder, but only two presented with chorea. Positron emission tomography and magnetic resonance volumetry revealed reduced striatal 2‐fluoro‐2‐deoxy‐glucose (FDG) uptake and diminished volumes of the caudate nucleus and putamen that correlated with disease duration. In contrast, none of 12 female mutation carriers showed psychiatric or movement disorders. However, a semidominant effect of the mutation was suggested by erythrocyte and blood group mosaicism and reduced striatal FDG uptake without structural abnormalities. Therefore, patients with psychiatric signs or symptoms segregating in an X‐linked trait should be examined for acanthocytosis and Kell/Kx blood group serology. Ann Neurol 2001;49:384–392

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

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

Comparison of MRI-Compatible Mechatronic Systems With Hydrodynamic and Pneumatic Actuation

The strong magnetic fields and limited space make it challenging to design the actuation for mechatronic systems intended to work in MRI environments. Hydraulic and pneumatic actuators can be made MRI-compatible and are promising solutions to drive robotic devices inside MRI environments. In this paper, two comparable haptic interface devices, one with hydrodynamic and another with pneumatic actuation, were developed to control one-degree-of-freedom translational movements of a user performing functional MRI (fMRI) tasks. The cylinders were made of MRI-compatible materials. Pressure sensors and control valves were placed far away from the end-effector in the scanner, connected via long transmission lines. It has been demonstrated that both manipulandum systems were MRI-compatible and yielded no artifacts to fMRI images in a 3-T scanner. Position and impedance controllers achieved passive as well as active subject movements. With the hydrodynamic system we have achieved smoother movements, higher position control accuracy, and improved robustness against force disturbances than with the pneumatic system. In contrast, the pneumatic system was back-drivable, showed faster dynamics with relatively low pressure, and allowed force control. Furthermore, it is easier to maintain and does not cause hygienic problems after leakages. In general, pneumatic actuation is more favorable for fast or force-controlled MRI-compatible applications, whereas hydrodynamic actuation is recommended for applications that require higher position accuracy, or slow and smooth movements.