Deep Brain Nuclei Research Articles

Brain Iron Accumulation in Atypical Parkinsonian Syndromes: in vivo MRI Evidences for Distinctive Patterns.

Recent data suggest mechanistic links among perturbed iron homeostasis, oxidative stress, and misfolded protein aggregation in neurodegenerative diseases. Iron overload and toxicity toward dopaminergic neurons have been established as playing a role in the pathogenesis of Parkinson's disease (PD). Brain iron accumulation has also been documented in atypical parkinsonian syndromes (APS), mainly comprising multiple system atrophy (MSA), and progressive supranuclear palsy (PSP). Iron-sensitive magnetic resonance imaging (MRI) has been applied to identify iron-related signal changes for the diagnosis and differentiation of these disorders. Topographic patterns of widespread iron deposition in deep brain nuclei have been described as differing between patients with MSA and PSP and those with PD. A disease-specific increase of iron occurs in the brain regions mainly affected by underlying disease pathologies. However, whether iron changes are a primary pathogenic factor or an epiphenomenon of neuronal degeneration has not been fully elucidated. Moreover, the clinical implications of iron-related pathology in APS remain unclear. In this review study, we collected data from qualitative and quantitative MRI studies on brain iron accumulation in APS to identify disease-related patterns and the potential role of iron-sensitive MRI.

Cognitive training benefit depends on brain injury location in adolescents with traumatic brain injury: a pilot study.

Executive dysfunction after pediatric traumatic brain injury (TBI) has been linked to poor outcomes in school performance, social functioning and employment. The credibility of training-induced cognitive enhancement in TBI is threatened by its limited proof of benefit in executive skills of daily living. Our primary aim was to investigate if cognitive intervention for improving impairments in executive functions in the chronic stage of TBI is effective during adolescence. The secondary aim was to explore whether training benefit is driven by injury location. Prospective observational study. Child Rehabilitation Center of a University Hospital. Sixteen adolescents with moderate to severe TBI (mean age 15 years and 8 months) and 16 age and gender matched healthy peers were included. Effects of a new cognitive training program (BrainGames) were assessed postintervention and 6 months later utilizing a comprehensive neuropsychological test-battery and the Behavior Rating Inventory of Executive Function. In addition, subgroup analyses were performed to determine long-term training benefit in the presence of lesions in corpus callosum, deep-brain-nuclei and prefrontal cortex. Adolescents with TBI showed significant improvements on measures of executive functioning at completion of the training and at follow-up compared with the pre-tests. The presence or absence of diffuse-axonal-injuries (DAI) in the deep brain nuclei determined a significant difference in long-term training benefit. This study provides preliminary evidence that cognitive training, beyond the acute rehabilitation period in adolescents with TBI is effective to boost executive functioning in daily living. Furthermore, we indicated that DAI in deep brain nuclei may jeopardize long-term benefit from cognitive training. Individualized rehabilitation programs are crucial in adolescents with different locations of TBI-lesions. Long term follow-up of pediatric TBI is essential.

Spatiotemporal Pattern of Gadodiamide-Related T1 Hyperintensity Increase Within the Deep Brain Nuclei.

The purpose of the study was to systematically evaluate the precise spatial and temporal pattern of gadolinium-related changes in T1-weighted signal intensity on unenhanced magnetic resonance (MR) images, occurring in the deep brain nuclei of adult patients exposed to at least 10 consecutive doses of gadodiamide. In this monocentric retrospective longitudinal study, we analyzed the brain MR images of 30 patients (12 women, 18 men; mean age, 43 ± 11.6 years) acquired between December 1998 and March 2008. We drew the regions of interest in the dentate nucleus, globus pallidus, putamen, pulvinar, ventral posterior nucleus of the thalamus, superior colliculus, substantia nigra, and white matter on unenhanced T1-weighted images. Each region of interest's mean signal intensity was normalized by the mean intensity of the pons. The normalized signal intensities were measured at the baseline before first gadodiamide administration and at each of 10 successive MR imaging examinations. We used linear mixed effects models to analyze the data. We observed a significant linear increase of signal intensity ratios across 10 successive gadodiamide administrations (all basal nuclei were significant at P < 0.001, except the ventral posterior thalamus, where P < 0.05), with the fastest signal intensity increase in the dentate nucleus (B = 0.010), followed by the globus pallidus (B = 0.0068), putamen (B = 0.0063), pulvinar (B = 0.0062), superior colliculus (B = 0.0057), substantia nigra (B = 0.0034), and ventral posterior nucleus of the thalamus (B = 0.0031). No significant signal increase was observed in the white matter (P > 0.05). Multiple consecutive administration of gadodiamide is associated with an increase in T1-weighted hypersignal on the unenhanced scans, displaying a gradual and nonuniform pattern across different deep brain nuclei, including the ventral posterior thalamus, which was used as a reference tissue in previous studies.

Standardized assessment of the signal intensity increase on unenhanced T1-weighted images in the brain: the European Gadolinium Retention Evaluation Consortium (GREC) Task Force position statement.

After the initial report in 2014 on T1-weighted (T1w) hyperintensity of deep brain nuclei following serial injections of linear gadolinium-based contrast agents (GBCAs), a multitude of studies on the potential of the marketed GBCAs to cause T1w hyperintensity in the brain have been published. The vast majority of these studies found a signal intensity (SI) increase for linear GBCAs in the brain-first and foremost in the dentate nucleus-while no SI increase was found for macrocyclic GBCAs. However, the scientific debate about this finding is kept alive by the fact that SI differences do not unequivocally represent the amount of gadolinium retained. Since the study design of the SI measurement in various brain structures is relatively simple, MRI studies investigating gadolinium-dependent T1w hyperintensity are currently conducted at multiple institutions worldwide. However, methodological mistakes may result in flawed conclusions. In this position statement, we assess the methodological basis of the published retrospective studies and define quality standards for future studies to give guidance to the scientific community and to help identify studies with potentially flawed methodology and misleading results. KEY POINTS: • A multitude of studies has been published on the potential of the marketed GBCAs to cause T1w hyperintensity in the brain. • The gadolinium-dependent T1w hyperintensity in the brain depends on patient's history, types of GBCAs used (i.e., linear vs. macrocyclic GBCAs) and MR imaging setup and protocols. • Quality standards for the design of future studies are needed to standardize methodology and avoid potentially misleading results from retrospective studies.

Comparison of subthalamic nucleus planning coordinates in 1Tesla and 3Tesla MRI for deep brain stimulation targeting

Deep brain stimulation (DBS) involves placing electrodes within specific deep brain nuclei. For movement disorders the most common indications are tremors, Parkinsons disease and dystonias. Surgeons mostly employ MR imaging for preoperative target selection. MR field geometrical distortion may contribute to target-selection error in the MR scan which can contribute to error in electrode placement. In this paper we compared the STN target planning coordinates in six parkinsonian DBS patients. Each patient underwent target planning in 1T and 3T MRI. We statistically compared and analysed the target-, and the fiducial coordinates in two different magnetic fileds. The target coordinates showed no significant differences (Mann-Whitney test, p > 0.05), however we found significant difference in fiducial coordinates (p < 0.01), in 3T MRI it was more pronounced (mean ± SD: 0.8 ± 0.3 mm) comparing to 1T (mean ± SD: 0.4 ± 0.2 mm). Preliminary results showed no significant differences in planning of target coordinates comparing 1T to 3T magnetic fields.

Real-time simultaneous recording of electrophysiological activities and dopamine overflow in the deep brain nuclei of a non-human primate with Parkinson\u2019s disease using nano-based microelectrode arrays

Parkinson’s disease (PD) is characterized by a progressive degeneration of nigrostriatal dopaminergic neurons. The precise mechanisms are still unknown. Since the neuronal communications are inherently electrical and chemical in nature, dual-mode detection of PD-related neuroelectrical and neurochemical information is essential for PD research. Subthalamic nucleus (STN) high-frequency stimulation (HFS) can improve most symptoms of PD patients and decrease the dosage of antiparkinsonian drugs. The mechanism of STN-HFS for PD still remains elusive. In this study, a silicon-based dual-mode microelectrode array (MEA) probe was designed and fabricated, and systematic dual-mode detection methods were established. The recording sites were modified using Pt nanoparticles and Nafion to improve the signal-to-noise (SNR) ratio. To evaluate its applicability to PD research, in vivo electrophysiological and electrochemical detection was performed in normal and hemiparkinsonian models, respectively. Through comparison of the dual-mode signals, we demonstrated the following in a PD monkey: (1) the maximum dopamine concentration in the striatum decreased by 90%; (2) the spike firing frequency increased significantly, especially in the region of the cortex; (3) the spectrogram analysis showed that much power existed in the 0–10 Hz frequency band; and (4) following repeated subthalamic nucleus high-frequency stimulation trials, the level of DA in the striatum increased by 16.5 μM, which led to a better elucidation of the mechanism of HFS. The dual-mode MEA probe was demonstrated to be an effective tool for the study of neurological disorders.

Parkinson's disease: diffusion kurtosis imaging and the correlation with clinical manifestations

Objective: Using magnetic resonance diffusion kurtosis imaging (DKI) to evaluate the microstructure changes of deep brain nucleus in Parkinson's disease (PD) as well as the correlation with clinical manifestations. Methods: Thirty-two PD patients were recruited into this study. Twenty gender and age matched healthy subjects served as the control group. All participants underwent MRI examinations, including T(1)WI, T(2)WI, DWI, susceptibility weighted imaging (SWI) and DKI. The original DKI imaging data were processed offline to calculate two parametric maps, including mean kurtosis (MK) value and fractional anisotropy (FA) value. Two DKI parameters measured from head of substantia nigra were compared between the two groups using t-test or Mann-Whitney U test according to data distribution. The correlations of the two DKI parameters in the substantia nigra of PD patients with the disease duration and clinical scales were tested by Spearmen or Pearson analysis according to data distribution. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of MK value in the substantia nigra for PD. Results: MK value in the substantia nigra of PD group (1.29±0.05) was significant higher than that of the control group (1.26±0.06) (t=2.24, P=0.03). There was no significant difference in FA value between the two groups. Spearmen correlation analysis revealed that there was no significant association of two DKI parameters in substantia nigra of PD patients with the disease duration and clinical scales. Conclusion: MR DKI of deep brain nucleuses can be useful for the diagnosis of PD, but it is not suitable to evaluate the degree of PD clinical symptoms.

Deep Brain Nuclei T1 Shortening after Gadobenate Dimeglumine in Children: Influence of Radiation and Chemotherapy

Intrinsic T1-hyperintense signal has recently been reported in the deep gray nuclei on brain MR imaging after multiple doses of gadolinium-based contrast agents. Most reports have included adult patients and excluded those undergoing radiation or chemotherapy. We investigated whether T1 shortening is also observed in children and tried to determine whether radiochemotherapy is a risk factor for this phenomenon. In this single-center retrospective study, we reviewed clinical charts and images of all patients 18 years of age or younger with ≥4 gadobenate dimeglumine-enhanced MRIs for 6 years. Seventy-six children (mean age, 9.3 years; 60 unconfounded by treatment, 16 with radiochemotherapy) met the selection criteria (>4 MR imaging examinations; mean, 8). T1 signal intensity ratios for the dentate to pons and globus pallidus to thalamus were calculated and correlated with number of injections, time interval, and therapy. Among the 60 children without radiochemotherapy, only 2 had elevated T1 signal intensity ratios (n = 20 and 16 injections). Twelve of the 16 children with radiochemotherapy showed elevated signal intensity ratios. Statistical analysis demonstrated a significant signal intensity ratio change for the number of injections (P < .001) and amount of gadolinium (P = .008), but not for the interscan time interval (P = .35). There was a significant difference in the average signal intensity ratio change between those with and without radiochemotherapy (P < .001). Chart review revealed no new neurologic deficits in any patients, related to their underlying conditions and prior surgeries. Compared with published adult series, children show a similar pattern of T1 hyperintense signal changes of the dentate and globus pallidus after multiple gadobenate dimeglumine injections. The T1 signal changes in children may have a later onset but are accelerated by radiochemotherapy.

Up to 52 administrations of macrocyclic ionic MR contrast agent are not associated with intracranial gadolinium deposition: Multifactorial analysis in 385 patients.

PurposeTo determine whether multiple repeated administrations of gadolinium-based macrocyclic ionic MR contrast agent (MICA) are associated with intracranial gadolinium deposition and identify the predisposing factors for deposition in various clinical situations.Materials and methodsIn this institutional review board-approved retrospective study, 385 consecutive patients who underwent MICA-enhanced MR imaging were enrolled. The dentate nucleus-to-pons (DN/P) and globus pallidus-to-thalamus (GP/Th) signal intensity (SI) ratios on unenhanced T1-weighted images were recorded by 2 independent readers and averaged. The mean DN/P and GP/Th SI ratio difference between the last and the first examinations were tested using the one-sample t-test. Student’s t-test and stepwise regression analysis were used to identify the predisposing factors for deposition based on the number of administrations, time interval, hepatic and renal function, magnetic field strength, and chemo- or radiation therapy.ResultsThe mean DN/P SI ratio difference was not different from zero (P = .697), even in patients with ≥20 administrations (n = 33). Only patients with abnormal renal function showed an increase in the mean DN/P SI ratio difference (P = .019). The mean DN/P SI ratio difference was not associated with any predisposing factors. However, the mean GP/Th SI ratio difference showed decrease (P < .001), which was associated with age (P = .007), number of administrations (P = .01) and number of radiation therapy sessions (P = .022) on multivariate analysis.ConclusionMultiple repeated administrations of MICA were not associated with increased T1 signal intensity in deep brain nuclei suggestive of Gd deposition in patients with normal renal function.

Iron in deep brain nuclei in migraine? CAMERA follow-up MRI findings.

Introduction In the CAMERA population-based MRI study, migraineurs below the age of 50 had decreased T2-values indicative of increased iron deposition in several deep brain nuclei. Longer migraine history was associated with lower T2-values, suggesting an association between migraine attacks and iron accumulation. In the present nine-year follow-up study of the CAMERA cohort we re-measured the T2-values in deep brain nuclei to assess the evolution over time. Methods Baseline and follow-up T2-values measured in several basal ganglia of 128 participants (38 control, 90 migraine) were analyzed using quantitative T2 measurements and multivariate regression analysis. Results T2-values of most deep brain nuclei were increased - instead of an expected further decrease when only age-related iron accumulation would have played a role - compared to baseline (both among controls and migraineurs) and were not different in either group. In migraineurs, no differences were found by gender, migraine severity or subtype. Conclusion This study did not provide supportive data for migraine related increased iron accumulation in deep brain nuclei, but neither is it able to reject such hypotheses. Increased T2-values probably point at microstructural tissue changes that counteracted earlier accumulated iron effects. We hypothesize that, with aging, migraine-induced iron-related brain changes are obscured by other age-related tissue changes.

The Use Of Nigrosin Staining To Increase Brain Slice Contrast For Neuroanatomy Teaching

Although plastic models and electronic resources play an important role in demonstrating concepts in neuroanatomy, the study of human cadaver brain remains important where it is necessary to illustrate detail, spatial relationships, or in clinical teaching. The most difficult structures to visualize in embalmed brains are the deep cerebral and cerebellar nuclei due to the muted contrast after embalming. Many contrast enhancing staining protocols have several drawbacks including vague published protocols, variability of staining, the need for counter‐stains, or the length of the staining process. The purpose of our study was to evaluate several simple stains and protocols that would be effective in increasing grey matter contrast in brain slices.Whole brains were extracted from cadavers fixed with 65% ethanol, 10% propylene glycol, 4% phenol, 4% Dettol and 2% formalin after 10–12 months. Brains were postfixed with 10% formalin for 2–3 weeks before use. Two Plexiglas frames were constructed with horizontal (transverse) or vertical (coronal) slits spaced 1 cm apart to facilitate the cutting of serial sections. Serial transverse or coronal slices of brains were washed in tap water for 1 min prior to staining. Brain slices were stained in various dilutions of aqueous toluidine blue, cresyl violet, or Nigrosin. The contrast between grey and white matter was measured with a standardized camera and image analysis was performed on 8‐bit images using Image‐J. Overstained or understained sections were obtained with all protocols except Nigrosin. The most successful staining was obtained on sections stained with 0.5% aqueous Nigrosin for 15 min followed by clearing in a series of water and ethanol rinses. Sections were stored on a stainless steel tray covered with a moist cloth for various times before quantitative analyses was performed. The depth of staining was evaluated in sections cut tangential to the stained surface. The robustness of the staining was evaluated in sections stored in water, 2% aqueous glycerol, 100% ethanol, or 100% acetone for various times up to 4 wks.We conclude that the staining of brain sections with Nigrosin provides high contrast differentiation of grey and white matter. Interestingly, details of white matter tracts became visible but certain deep brain nuclei were consistently unstained. There was minimal fading of the staining after storage in organic and inorganic solvents indicating that the method may be useful for long term storage as both wet or plastinated specimens. Nigrosin staining of brain slices serves as a simple method to increase the visibility of brain structures for the study of neuroanatomy.Support or Funding InformationEducation Program in Anatomy, McMaster University

Motor associations of iron accumulation in deep grey matter nuclei in Parkinson's disease: a cross-sectional study of iron-related magnetic resonance imaging susceptibility.

To determine whether iron deposition in deep brain nuclei assessed using high-pass filtered phase imaging plays a role in motor disease severity in Parkinson's disease (PD). Seventy patients with mild to moderate PD and 20 age- and gender-matched healthy volunteers (HVs) underwent susceptibility-weighted imaging on a 3 T magnetic resonance imaging scanner. Phase shifts (radians) in deep brain nuclei were derived from high-pass filtered phase images and compared between groups. Analysis of clinical laterality and correlations with motor severity (Unified Parkinson's Disease Rating Scale, Part III, UPDRS-III) were performed. Phase shifts (in radians) were compared between HVs and three PD subgroups divided according to UPDRS-III scores using analysis of covariance, adjusting for age and regional area. Parkinson's disease patients had significantly (P < 0.001) higher radians than HVs bilaterally in the putamen, globus pallidus and substantia nigra (SN). The SN contralateral to the most affected side showed higher radians (P < 0.001) compared to the less affected side. SN radians positively correlated with UPDRS-III and bradykinesia-rigidity subscores, but not with tremor subscores. ancova followed by post hoc Bonferroni-adjusted pairwise comparisons revealed that SN radians were significantly greater in the PD subgroup with higher UPDRS-III scores compared to both lowest UPDRS-III PD and HV groups (P < 0.001). Increased nigral iron accumulation in PD appears to be stratified according to disease motor severity and correlates with symptoms related to dopaminergic neurodegeneration. This semi-quantitative in vivo iron assessment could prove useful for objectively monitoring PD progression, especially in clinical trials concerning iron chelation therapies.

Comparison of Two Quantitative Susceptibility Mapping Measurement Methods Used For Anatomical Localization of the Iron-Incorporated Deep Brain Nuclei

Introduction Quantitative susceptibility mapping (QSM) is a new contrast mechanism in magnetic resonance imaging (MRI). The images produced by the QSM enable researchers and clinicians to easily localize specific structures of the brain, such as deep brain nuclei. These nuclei are targets in many clinical applications and therefore their easy localization is a must. In this study, we aimed to implement two QSM estimation algorithms, threshold-based k-space division (TKD) and morphology enabled dipole inversion (MEDI) in presurgical planning. Materials and Methods In this study, susceptibility weighted imaging (SWI) was performed on six patients referred to our center for presurgical planning purposes. The susceptibility values, as well as the contrast-to-noise ratio of few brain regions were estimated. To identify the algorithm, which was best applicable to clinics, a comparison of the two methods was performed. Results QSM images were produced; however, the results did not show any significant differences between the susceptibility values of the two methods. The contrast-to-noise ratio for the susceptibility values of the subthalamic nucleus and substantia nigra brain regions were significantly superior using the MEDI approach over TKD, suggesting improved localization of brain regions using the former method. Conclusion This study suggests that to identify specific brain regions, such as deep brain nuclei, a QSM contrast would be more beneficial than the conventional MRI contrasts. This study compared MEDI and TKD methods for quantification of brain susceptibility maps, and results showed that the MEDI method resulted in higher-quality images.

Effect of Renal Function on Gadolinium-Related Signal Increases on Unenhanced T1-Weighted Brain Magnetic Resonance Imaging.

The purpose of this study was to determine if renal function affects signal changes in the deep brain nuclei on unenhanced T1-weighted images after administration of linear gadolinium-based contrast agents (GBCAs). An electronic medical records search of 2 large medical centers identified 25 patients who received linear GBCA while on hemodialysis and had unenhanced T1-weighted images of the brain before and after. The dentate-to-cerebellar peduncle (DCP) ratio, globus pallidus-to-mid thalamus (GPT) ratio, and choroid plexus-to-nearby white matter ratio were measured and compared with 25 age/sex/GBCA exposure-matched control patients with normal or near-normal renal function (estimated glomerular filtration rate >60 mL/min per 1.73 m). Two additional control groups included 13 patients on hemodialysis without GBCA exposure and 13 age/sex-matched patients with estimated glomerular filtration rate greater than 60 mL/min per 1.73 m. Hemodialysis patients (n = 25) with an average of 1.8 linear GBCA administrations had a 4.9% mean increase (1.00 ± 0.04 vs 1.05 ± 0.05; P < 0.001) in DCP, which was greater than the 1.6% change (0.99 ± 0.04 vs 1.00 ± 0.05; P = 0.08) observed in matched controls (P = 0.01). There was no significant signal change in the DCP ratio in the 13 hemodialysis patients (0.99 ± 0.04 vs 0.99 ± 0.04; P = 0.78) and 13 age/sex-matched patients (0.99 ± 0.02 vs 0.99 ± 0.03; P = 0.78) who did not receive GBCA. The hemodialysis patients had a baseline GPT that was higher than nondialysis patients (P < 0.001). However, the GPT change after GBCA administration was not significantly different from controls. Increased signal in the choroid plexus on unenhanced T1-weighted images after GBCA administration was noted in hemodialysis patients (0.72 ± 0.20 vs 0.86 ± 0.23; P = 0.006); however, a multivariate analysis showed this to be primarily related to hemodialysis (P = 0.003) with only a trend toward relating to GBCA exposure (P = 0.07). Hemodialysis patients receiving linear GBCA have greater dentate nucleus signal increases on unenhanced T1-weighted images, suggesting that renal function may affect the rate of gadolinium accumulation in the brain after linear GBCA-enhanced magnetic resonance imaging.

A silicon based implantable microelectrode array for electrophysiological and dopamine recording from cortex to striatum in the non-human primate brain

Dual-mode, multielectrode recordings have become routine in rodent neuroscience research and have recently been adapted to the non-human primate. However, robust and reliable application of acute, multielectrode recording methods in monkeys especially for deep brain nucleus research remains a challenge. In this paper, We described a low cost silicon based 16-site implantable microelectrode array (MEA) chip fabricated by standard lithography technology for in vivo test. The array was 25mm long and designed to use in non-human primate models, for electrophysiological and electrochemical recording. We presented a detailed protocol for array fabrication, then showed that the device can record Spikes, LFPs and dopamine (DA) variation continuously from cortex to striatum in an esthetized monkey. Though our experiment, high-quality electrophysiological signals were obtained from the animal. Across any given microelectrode, spike amplitudes ranged from 70 to 300μV peak to peak, with a mean signal-to-noise ratio of better than 5:1. Calibration results showed the MEA probe had high sensitivity and good selectivity for DA. The DA concentration changed from 42.8 to 481.6μM when the MEA probe inserted from cortex into deep brain nucleus of striatum, which reflected the inhomogeneous distribution of DA in brains. Compared with existing methods allowing single mode (electrophysiology or electrochemistry) recording. This system is designed explicitly for dual-mode recording to meet the challenges of recording in non-human primates.

In Vivo MRI Mapping of Brain Iron Deposition across the Adult Lifespan.

This study used a whole--brain imaging approach known as quantitative susceptibility mapping (QSM) to provide a novel insight into iron accumulation in the brain across the adult lifespan. Validity of the method was demonstrated by showing concordance with ROI analysis and prior knowledge of iron accumulation in subcortical nuclei. We discovered that, beyond these regions, there is extensive involvement of the frontal lobes that has been missed by past ROI analyses. Broadly speaking, therefore, the motor system selectively accumulates iron with age. The results offer insights into the aging process, but also offer a new approach to studying the role of iron dysregulation in the evolution of age-related neurodegenerative diseases.

Segmentation of human brain using structural MRI.

Segmentation of human brain using structural MRI is a key step of processing in imaging neuroscience. The methods have undergone a rapid development in the past two decades and are now widely available. This non-technical review aims at providing an overview and basic understanding of the most common software. Starting with the basis of structural MRI contrast in brain and imaging protocols, the concepts of voxel-based and surface-based segmentation are discussed. Special emphasis is given to the typical contrast features and morphological constraints of cortical and sub-cortical grey matter. In addition to the use for voxel-based morphometry, basic applications in quantitative MRI, cortical thickness estimations, and atrophy measurements as well as assignment of cortical regions and deep brain nuclei are briefly discussed. Finally, some fields for clinical applications are given.

Deep Brain Stimulation: Awake and Asleep Options

“Good stereotactic surgery for movement disorders can be performed with or without the microelectrode, and poor surgical results can occur both with and without the microelectrode.” – Dr. Roy Bakay1 A BRIEF HISTORY OF DBS AND NEUROIMAGING Stereotactic neurosurgery is founded on the ability to accurately localize and safely access targets within the brain in a minimally-invasive manner. The stereotactic method was first described in 1908 by Sir Victor Horsley and Robert Clarke at University College London, where they developed an apparatus for animal experimentation that allowed them to establish a threedimensional Cartesian coordinate system for targeting. At that time, however, x-rays were the only available form of imaging the human body and as such, localizing intracranial targets relied on a combination of knowledge from anatomical atlases and the visualization of a few intracranial landmarks such as the pineal gland or the foramen of Monroe. These landmarks could be visualized by filling the ventricles with air (pneumoencephalogram) or a contrast medium (ventriculogram) [Figure 1]. In 1947, Ernst Spiegel and Henry Wycis created the first human stereotactic frame that allowed for lesioning of deep brain nuclei for the treatment of psychiatric disease.2

Clinical feasibility of using mean apparent propagator (MAP) MRI to characterize brain tissue microstructure

Diffusion tensor imaging (DTI) is the most widely used method for characterizing noninvasively structural and architectural features of brain tissues. However, the assumption of a Gaussian spin displacement distribution intrinsic to DTI weakens its ability to describe intricate tissue microanatomy. Consequently, the biological interpretation of microstructural parameters, such as fractional anisotropy or mean diffusivity, is often equivocal. We evaluate the clinical feasibility of assessing brain tissue microstructure with mean apparent propagator (MAP) MRI, a powerful analytical framework that efficiently measures the probability density function (PDF) of spin displacements and quantifies useful metrics of this PDF indicative of diffusion in complex microstructure (e.g., restrictions, multiple compartments). Rotation invariant and scalar parameters computed from the MAP show consistent variation across neuroanatomical brain regions and increased ability to differentiate tissues with distinct structural and architectural features compared with DTI-derived parameters. The return-to-origin probability (RTOP) appears to reflect cellularity and restrictions better than MD, while the non-Gaussianity (NG) measures diffusion heterogeneity by comprehensively quantifying the deviation between the spin displacement PDF and its Gaussian approximation. Both RTOP and NG can be decomposed in the local anatomical frame for reference determined by the orientation of the diffusion tensor and reveal additional information complementary to DTI. The propagator anisotropy (PA) shows high tissue contrast even in deep brain nuclei and cortical gray matter and is more uniform in white matter than the FA, which drops significantly in regions containing crossing fibers. Orientational profiles of the propagator computed analytically from the MAP MRI series coefficients allow separation of different fiber populations in regions of crossing white matter pathways, which in turn improves our ability to perform whole-brain fiber tractography. Reconstructions from subsampled data sets suggest that MAP MRI parameters can be computed from a relatively small number of DWIs acquired with high b-value and good signal-to-noise ratio in clinically achievable scan durations of less than 10min. The neuroanatomical consistency across healthy subjects and reproducibility in test–retest experiments of MAP MRI microstructural parameters further substantiate the robustness and clinical feasibility of this technique. The MAP MRI metrics could potentially provide more sensitive clinical biomarkers with increased pathophysiological specificity compared to microstructural measures derived using conventional diffusion MRI techniques.

Investigation of Parallel Radiofrequency Transmission for the Reduction of Heating in Long Conductive Leads in 3 Tesla Magnetic Resonance Imaging.

Deep Brain Stimulation (DBS) is increasingly used to treat a variety of brain diseases by sending electrical impulses to deep brain nuclei through long, electrically conductive leads. Magnetic resonance imaging (MRI) of patients pre- and post-implantation is desirable to target and position the implant, to evaluate possible side-effects and to examine DBS patients who have other health conditions. Although MRI is the preferred modality for pre-operative planning, MRI post-implantation is limited due to the risk of high local power deposition, and therefore tissue heating, at the tip of the lead. The localized power deposition arises from currents induced in the leads caused by coupling with the radiofrequency (RF) transmission field during imaging. In the present work, parallel RF transmission (pTx) is used to tailor the RF electric field to suppress coupling effects. Electromagnetic simulations were performed for three pTx coil configurations with 2, 4, and 8-elements, respectively. Optimal input voltages to minimize coupling, while maintaining RF magnetic field homogeneity, were determined for all configurations using a Nelder-Mead optimization algorithm. Resulting electric and magnetic fields were compared to that of a 16-rung birdcage coil. Experimental validation was performed with a custom-built 4-element pTx coil. In simulation, 95-99% reduction of the electric field at the tip of the lead was observed between the various pTx coil configurations and the birdcage coil. Maximal reduction in E-field was obtained with the 8-element pTx coil. Magnetic field homogeneity was comparable to the birdcage coil for the 4- and 8-element pTx configurations. In experiment, a temperature increase of 2±0.15°C was observed at the tip of the wire using the birdcage coil, whereas negligible increase (0.2±0.15°C) was observed with the optimized pTx system. Although further research is required, these initial results suggest that the concept of optimizing pTx to reduce DBS heating effects holds considerable promise.