Publications

@article{Voigt2023,

title = {Reflective multi-immersion microscope objectives inspired by the Schmidt telescope},

author = {Fabian F. Voigt and Anna Maria Reuss and Thomas Naert and Sven Hildebrand and Martina Schaettin and Adriana L. Hotz and Lachlan Whitehead and Armin Bahl and Stephan C. F. Neuhauss and Alard Roebroeck and Esther T. Stoeckli and Soeren S. Lienkamp and Adriano Aguzzi and Fritjof Helmchen},

url = {https://www.nature.com/articles/s41587-023-01717-8},

doi = {10.1038/s41587-023-01717-8},

issn = {1546-1696},

year  = {2023},

date = {2023-03-01},

journal = {Nature Biotechnology 2023},

pages = {1--7},

publisher = {Nature Publishing Group},

abstract = {Imaging large, cleared samples requires microscope objectives that combine a large field of view (FOV) with a long working distance (WD) and a high numerical aperture (NA). Ideally, such objectives should be compatible with a wide range of immersion media, which is challenging to achieve with conventional lens-based objective designs. Here we introduce the multi-immersion ‘Schmidt objective' consisting of a spherical mirror and an aspherical correction plate as a solution to this problem. We demonstrate that a multi-photon variant of the Schmidt objective is compatible with all homogeneous immersion media and achieves an NA of 1.08 at a refractive index of 1.56, 1.1-mm FOV and 11-mm WD. We highlight its versatility by imaging cleared samples in various media ranging from air and water to benzyl alcohol/benzyl benzoate, dibenzyl ether and ethyl cinnamate and by imaging of neuronal activity in larval zebrafish in vivo. In principle, the concept can be extended to any imaging modality, including wide-field, confocal and light-sheet microscopy. Imaging of large, cleared samples in diverse media is achieved using a mirror objective.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Schueth2023,

title = {Efficient 3D light-sheet imaging of very large-scale optically cleared human brain and prostate tissue samples.},

author = {Anna Schueth and Sven Hildebrand and Iryna Samarska and Shubharthi Sengupta and Annemarie Kiessling and Andreas Herrler and Axel Zur Hausen and Michael Capalbo and Alard Roebroeck},

doi = {10.1038/s42003-023-04536-4},

issn = {2399-3642 (Electronic)},

year  = {2023},

date = {2023-02-01},

journal = {Communications biology},

volume = {6},

number = {1},

pages = {170},

abstract = {The ability to image human tissue samples in 3D, with both cellular resolution and a large field of view (FOV), can improve fundamental and clinical investigations. Here, we demonstrate the feasibility of light-sheet imaging of $sim$5 cm(3) sized formalin fixed human brain and up to $sim$7 cm(3) sized formalin fixed paraffin embedded (FFPE) prostate cancer samples, processed with the FFPE-MASH protocol. We present a light-sheet microscopy prototype, the cleared-tissue dual view Selective Plane Illumination Microscope (ct-dSPIM), capable of fast 3D high-resolution acquisitions of cm(3) scale cleared tissue. We used mosaic scans for fast 3D overviews of entire tissue samples or higher resolution overviews of large ROIs with various speeds: (a) Mosaic 16 (16.4 µm isotropic resolution, $sim$1.7 h/cm(3)), (b) Mosaic 4 (4.1 µm isotropic resolution, $sim$ 5 h/cm(3)) and (c) Mosaic 0.5 (0.5 µm near isotropic resolution, $sim$15.8 h/cm(3)). We could visualise cortical layers and neurons around the border of human brain areas V1&V2, and could demonstrate suitable imaging quality for Gleason score grading in thick prostate cancer samples. We show that ct-dSPIM imaging is an excellent technique to quantitatively assess entire MASH prepared large-scale human tissue samples in 3D, with considerable future clinical potential.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pimpini2022,

title = {More complex than you might think: Neural representations of food reward value in obesity.},

author = {Leonardo Pimpini and Sarah Kochs and Sieske Franssen and Job Hurk and Giancarlo Valente and Alard Roebroeck and Anita Jansen and Anne Roefs},

doi = {10.1016/j.appet.2022.106164},

issn = {1095-8304 (Electronic)},

year  = {2022},

date = {2022-11-01},

journal = {Appetite},

volume = {178},

pages = {106164},

abstract = {Obesity reached pandemic proportions and weight-loss treatments are mostly ineffective. The level of brain activity in the reward circuitry is proposed to be proportionate to the reward value of food stimuli, and stronger in people with obesity. However, empirical evidence is inconsistent. This may be due to the double-sided nature of high caloric palatable foods: at once highly palatable and high in calories (unhealthy). This study hypothesizes that, viewing high caloric palatable foods, a hedonic attentional focus compared to a health and a neutral attentional focus elicits more activity in reward-related brain regions, mostly in people with obesity. Moreover, caloric content and food palatability can be decoded from multivoxel patterns of activity most accurately in people with obesity and in the corresponding attentional focus. During one fMRI-session, attentional focus (hedonic, health, neutral) was manipulated using a one-back task with individually tailored food stimuli in 32 healthy-weight people and 29 people with obesity. Univariate analyses (p < 0.05, FWE-corrected) showed that brain activity was not different for palatable vs. unpalatable foods, nor for high vs. low caloric foods. Instead, this was higher in the hedonic compared to the health and neutral attentional focus. Multivariate analyses (MVPA) (p < 0.05, FDR-corrected) showed that palatability and caloric content could be decoded above chance level, independently of either BMI or attentional focus. Thus, brain activity to visual food stimuli is neither proportionate to the reward value (palatability and/or caloric content), nor significantly moderated by BMI. Instead, it depends on people's attentional focus, and may reflect motivational salience. Furthermore, food palatability and caloric content are represented as patterns of brain activity, independently of BMI and attentional focus. So, food reward value is reflected in patterns, not levels, of brain activity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wang2022,

title = {Inconsistencies in atlas-based volumetric measures of the human nucleus basalis of Meynert: A need for high-resolution alternatives.},

author = {Yawen Wang and Minye Zhan and Alard Roebroeck and Peter De Weerd and Sriranga Kashyap and Mark J Roberts},

doi = {10.1016/j.neuroimage.2022.119421},

issn = {1095-9572 (Electronic)},

year  = {2022},

date = {2022-10-01},

journal = {NeuroImage},

volume = {259},

pages = {119421},

abstract = {The nucleus basalis of Meynert (nbM) is the major source of cortical acetylcholine (ACh) and has been related to cognitive processes and to neurological disorders. However, spatially delineating the human nbM in MRI studies remains challenging. Due to the absence of a functional localiser for the human nbM, studies to date have localised it using nearby neuroanatomical landmarks or using probabilistic atlases. To understand the feasibility of MRI of the nbM we set our four goals; our first goal was to review current human nbM region-of-interest (ROI) selection protocols used in MRI studies, which we found have reported highly variable nbM volume estimates. Our next goal was to quantify and discuss the limitations of existing atlas-based volumetry of nbM. We found that the identified ROI volume depends heavily on the atlas used and on the probabilistic threshold set. In addition, we found large disparities even for data/studies using the same atlas and threshold. To test whether spatial resolution contributes to volume variability, as our third goal, we developed a novel nbM mask based on the normalized BigBrain dataset. We found that as long as the spatial resolution of the target data was 1.3 mm isotropic or above, our novel nbM mask offered realistic and stable volume estimates. Finally, as our last goal we tried to discern nbM using publicly available and novel high resolution structural MRI ex vivo MRI datasets. We find that, using an optimised 9.4T quantitative T(2)(⁎) ex vivo dataset, the nbM can be visualised using MRI. We conclude caution is needed when applying the current methods of mapping nbM, especially for high resolution MRI data. Direct imaging of the nbM appears feasible and would eliminate the problems we identify, although further development is required to allow such imaging using standard (f)MRI scanning.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gooijers2022,

title = {Representational similarity scores of digits in the sensorimotor cortex are associated with behavioral performance.},

author = {J Gooijers and S Chalavi and L K Koster and A Roebroeck and A Kaas and S P Swinnen},

doi = {10.1093/cercor/bhab452},

issn = {1460-2199 (Electronic)},

year  = {2022},

date = {2022-08-01},

journal = {Cerebral cortex (New York, N.Y. : 1991)},

volume = {32},

number = {17},

pages = {3848--3863},

abstract = {Previous studies aimed to unravel a digit-specific somatotopy in the primary sensorimotor (SM1) cortex. However, it remains unknown whether digit somatotopy is associated with motor preparation and/or motor execution during different types of tasks. We adopted multivariate representational similarity analysis to explore digit activation patterns in response to a finger tapping task (FTT). Sixteen healthy young adults underwent magnetic resonance imaging, and additionally performed an out-of-scanner choice reaction time task (CRTT) to assess digit selection performance. During both the FTT and CRTT, force data of all digits were acquired using force transducers. This allowed us to assess execution-related interference (i.e., digit enslavement; obtained from FTT & CRTT), as well as planning-related interference (i.e., digit selection deficit; obtained from CRTT) and determine their correlation with digit representational similarity scores of SM1. Findings revealed that digit enslavement during FTT was associated with contralateral SM1 representational similarity scores. During the CRTT, digit enslavement of both hands was also associated with representational similarity scores of the contralateral SM1. In addition, right hand digit selection performance was associated with representational similarity scores of left S1. In conclusion, we demonstrate a cortical origin of digit enslavement, and uniquely reveal that digit selection is associated with digit representations in primary somatosensory cortex (S1). Significance statement In current systems neuroscience, it is of critical importance to understand the relationship between brain function and behavioral outcome. With the present work, we contribute significantly to this understanding by uniquely assessing how digit representations in the sensorimotor cortex are associated with planning- and execution-related digit interference during a continuous finger tapping and a choice reaction time task. We observe that digit enslavement (i.e., execution-related interference) finds its origin in contralateral digit representations of SM1, and that deficits in digit selection (i.e., planning-related interference) in the right hand during a choice reaction time task are associated with more overlapping digit representations in left S1. This knowledge sheds new light on the functional contribution of the sensorimotor cortex to everyday motor skills.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{So2022,

title = {BUDA-MESMERISE: Rapid acquisition and unsupervised parameter estimation for T(1) , T(2) , M(0) , B(0) , and B(1) maps.},

author = {Seohee So and Hyun Wook Park and Byungjai Kim and Francisco J Fritz and Benedikt A Poser and Alard Roebroeck and Berkin Bilgic},

doi = {10.1002/mrm.29228},

issn = {1522-2594 (Electronic)},

year  = {2022},

date = {2022-07-01},

journal = {Magnetic resonance in medicine},

volume = {88},

number = {1},

pages = {292--308},

abstract = {PURPOSE: Rapid acquisition scheme and parameter estimation method are proposed to acquire distortion-free spin- and stimulated-echo signals and combine the signals with a physics-driven unsupervised network to estimate T(1) , T(2) , and proton density (M(0) ) parameter maps, along with B(0) and B(1) information from the acquired signals. THEORY AND METHODS: An imaging sequence with three 90° RF pulses is utilized to acquire spin- and stimulated-echo signals. We utilize blip-up/-down acquisition to eliminate geometric distortion incurred by the effects of B(0) inhomogeneity on rapid EPI acquisitions. For multislice imaging, echo-shifting is applied to utilize dead time between the second and third RF pulses to encode information from additional slice positions. To estimate parameter maps from the spin- and stimulated-echo signals with high fidelity, 2 estimation methods, analytic fitting and a novel unsupervised deep neural network method, are developed. RESULTS: The proposed acquisition provided distortion-free T(1) , T(2) , relative proton density (M0), B(0) , and B(1) maps with high fidelity both in phantom and in vivo brain experiments. From the rapidly acquired spin- and stimulated-echo signals, analytic fitting and the network-based method were able to estimate T(1) , T(2) , M(0) , B(0) , and B(1) maps with high accuracy. Network estimates demonstrated noise robustness owing to the fact that the convolutional layers take information into account from spatially adjacent voxels. CONCLUSION: The proposed acquisition/reconstruction technique enabled whole-brain acquisition of coregistered, distortion-free, T(1) , T(2) , M(0) , B(0) , and B(1) maps at 1 × 1 × 5 mm(3) resolution in 50 s. The proposed unsupervised neural network provided noise-robust parameter estimates from this rapid acquisition.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Franssen2022,

title = {Effects of mindset on hormonal responding, neural representations, subjective experience and intake.},

author = {Sieske Franssen and Anita Jansen and Job Hurk and Tanja Adam and Kelly Geyskens and Alard Roebroeck and Anne Roefs},

doi = {10.1016/j.physbeh.2022.113746},

issn = {1873-507X (Electronic)},

year  = {2022},

date = {2022-05-01},

journal = {Physiology & behavior},

volume = {249},

pages = {113746},

abstract = {A person can alternate between food-related mindsets, which in turn may depend on one's emotional state or situation. Being in a certain mindset can influence food-related thoughts, but interestingly it might also affect eating-related physiological responses. The current study investigates the influence of an induced 'loss of control' mindset as compared to an 'in control' mindset on hormonal, neural and behavioural responses to chocolate stimuli. Mindsets were induced by having female chocolate lovers view a short movie during two sessions in a within-subjects design. Neural responses to visual chocolate stimuli were measured using an ultra-high field (7T) scanner. Momentary ghrelin and glucagon-like peptide 1 (GLP-1) levels were determined on five moments and were simultaneously assessed with self-reports on perceptions of chocolate craving, hunger and feelings of control. Furthermore, chocolate intake was measured using a bogus chocolate taste test. It was hypothesized that the loss of control mindset would lead to hormonal, neural and behavioural responses that prepare for ongoing food intake, even after eating, while the control mindset would lead to responses reflecting satiety. Results show that neural activity in the mesocorticolimbic system was stronger for chocolate stimuli than for neutral stimuli and that ghrelin and GLP-1 levels responded to food intake, irrespective of mindset. Self-reported craving and actual chocolate intake were affected by mindset, in that cravings and intake were higher with a loss of control mindset than with a control mindset. Interestingly, these findings suggest that physiology on the one hand (hormonal and neural responses) and behavior and subjective experience (food intake and craving) on the other hand are not in sync, are not equally affected by mindset.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{VanLanen2022,

title = {Value of ultra-high field MRI in patients with suspected focal epilepsy and negative 3 T MRI (EpiUltraStudy): protocol for a prospective, longitudinal therapeutic study.},

author = {R H G J Lanen and C J Wiggins and A J Colon and W H Backes and J F A Jansen and D Uher and G S Drenthen and A Roebroeck and D Ivanov and B A Poser and M C Hoeberigs and S M J Kuijk and G Hoogland and K Rijkers and G L Wagner and J Beckervordersandforth and D Delev and H Clusmann and S Wolking and S Klinkenberg and R P W Rouhl and P A M Hofman and O E M G Schijns},

doi = {10.1007/s00234-021-02884-8},

issn = {1432-1920 (Electronic)},

year  = {2022},

date = {2022-04-01},

journal = {Neuroradiology},

volume = {64},

number = {4},

pages = {753--764},

abstract = {PURPOSE: Resective epilepsy surgery is a well-established, evidence-based treatment option in patients with drug-resistant focal epilepsy. A major predictive factor of good surgical outcome is visualization and delineation of a potential epileptogenic lesion by MRI. However, frequently, these lesions are subtle and may escape detection by conventional MRI (≤ 3 T). METHODS: We present the EpiUltraStudy protocol to address the hypothesis that application of ultra-high field (UHF) MRI increases the rate of detection of structural lesions and functional brain aberrances in patients with drug-resistant focal epilepsy who are candidates for resective epilepsy surgery. Additionally, therapeutic gain will be addressed, testing whether increased lesion detection and tailored resections result in higher rates of seizure freedom 1 year after epilepsy surgery. Sixty patients enroll the study according to the following inclusion criteria: aged ≥ 12 years, diagnosed with drug-resistant focal epilepsy with a suspected epileptogenic focus, negative conventional 3 T MRI during pre-surgical work-up. RESULTS: All patients will be evaluated by 7 T MRI; ten patients will undergo an additional 9.4 T MRI exam. Images will be evaluated independently by two neuroradiologists and a neurologist or neurosurgeon. Clinical and UHF MRI will be discussed in the multidisciplinary epilepsy surgery conference. Demographic and epilepsy characteristics, along with postoperative seizure outcome and histopathological evaluation, will be recorded. CONCLUSION: This protocol was reviewed and approved by the local Institutional Review Board and complies with the Declaration of Helsinki and principles of Good Clinical Practice. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: www.trialregister.nl : NTR7536.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gooijers2021,

title = {Indices of callosal axonal density and radius from diffusion MRI relate to upper and lower limb motor performance.},

author = {J Gooijers and A De Luca and H Zivari Adab and A Leemans and A Roebroeck and S P Swinnen},

doi = {10.1016/j.neuroimage.2021.118433},

issn = {1095-9572 (Electronic)},

year  = {2021},

date = {2021-11-01},

journal = {NeuroImage},

volume = {241},

pages = {118433},

abstract = {Understanding the relationship between human brain structure and functional outcome is of critical importance in systems neuroscience. Diffusion MRI (dMRI) studies show that fractional anisotropy (FA) is predictive of motor control, underscoring the importance of white matter (WM). However, as FA is a surrogate marker of WM, we aim to shed new light on the structural underpinnings of this relationship by applying a multi-compartment microstructure model providing axonal density/radius indices. Sixteen young adults (7 males / 9 females), performed a hand/foot tapping task and a Multi Limb Reaction Time task. Furthermore, diffusion (STEAM &HARDI) and fMRI (localizer hand/foot activations) data were obtained. Sphere ROIs were placed on activation clusters with highest t value to guide interhemispheric WM tractography. Axonal radius/density indices of callosal parts intersecting with tractography were calculated from STEAM, using the diffusion-time dependent AxCaliber model, and correlated with behavior. Results indicated a possible association between larger apparent axonal radii of callosal motor fibers of the hand and higher tapping scores of both hands, and faster selection-related processing (normalized reaction) times (RTs) on diagonal limb combinations. Additionally, a trend was present for faster selection-related processing (normalized reaction) times for lower limbs being related with higher axonal density of callosal foot motor fibers, and for higher FA values of callosal motor fibers in general being related with better tapping and faster selection-related processing (normalized reaction) times. Whereas FA is sensitive in demonstrating associations with motor behavior, axon radius/density (i.e., fiber geometry) measures are promising to explain the physiological source behind the observed FA changes, contributing to deeper insights into brain-behavior interactions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Belyk2021,

title = {Human larynx motor cortices coordinate respiration for vocal-motor control.},

author = {Michel Belyk and Rachel Brown and Deryk S Beal and Alard Roebroeck and Carolyn McGettigan and Stella Guldner and Sonja A Kotz},

doi = {10.1016/j.neuroimage.2021.118326},

issn = {1095-9572 (Electronic)},

year  = {2021},

date = {2021-10-01},

journal = {NeuroImage},

volume = {239},

pages = {118326},

abstract = {Vocal flexibility is a hallmark of the human species, most particularly the capacity to speak and sing. This ability is supported in part by the evolution of a direct neural pathway linking the motor cortex to the brainstem nucleus that controls the larynx the primary sound source for communication. Early brain imaging studies demonstrated that larynx motor cortex at the dorsal end of the orofacial division of motor cortex (dLMC) integrated laryngeal and respiratory control, thereby coordinating two major muscular systems that are necessary for vocalization. Neurosurgical studies have since demonstrated the existence of a second larynx motor area at the ventral extent of the orofacial motor division (vLMC) of motor cortex. The vLMC has been presumed to be less relevant to speech motor control, but its functional role remains unknown. We employed a novel ultra-high field (7T) magnetic resonance imaging paradigm that combined singing and whistling simple melodies to localise the larynx motor cortices and test their involvement in respiratory motor control. Surprisingly, whistling activated both 'larynx areas' more strongly than singing despite the reduced involvement of the larynx during whistling. We provide further evidence for the existence of two larynx motor areas in the human brain, and the first evidence that laryngeal-respiratory integration is a shared property of both larynx motor areas. We outline explicit predictions about the descending motor pathways that give these cortical areas access to both the laryngeal and respiratory systems and discuss the implications for the evolution of speech.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fritz2021,

title = {MESMERISED: Super-accelerating T(1) relaxometry and diffusion MRI with STEAM at 7 T for quantitative multi-contrast and diffusion imaging.},

author = {F J Fritz and B A Poser and A Roebroeck},

doi = {10.1016/j.neuroimage.2021.118285},

issn = {1095-9572 (Electronic)},

year  = {2021},

date = {2021-10-01},

journal = {NeuroImage},

volume = {239},

pages = {118285},

abstract = {There is an increasing interest in quantitative imaging of T(1), T(2) and diffusion contrast in the brain due to greater robustness against bias fields and artifacts, as well as better biophysical interpretability in terms of microstructure. However, acquisition time constraints are a challenge, particularly when multiple quantitative contrasts are desired and when extensive sampling of diffusion directions, high b-values or long diffusion times are needed for multi-compartment microstructure modeling. Although ultra-high fields of 7 T and above have desirable properties for many MR modalities, the shortening T(2) and the high specific absorption rate (SAR) of inversion and refocusing pulses bring great challenges to quantitative T(1), T(2) and diffusion imaging. Here, we present the MESMERISED sequence (Multiplexed Echo Shifted Multiband Excited and Recalled Imaging of STEAM Encoded Diffusion). MESMERISED removes the dead time in Stimulated Echo Acquisition Mode (STEAM) imaging by an echo-shifting mechanism. The echo-shift (ES) factor is independent of multiband (MB) acceleration and allows for very high multiplicative (ESxMB) acceleration factors, particularly under moderate and long mixing times. This results in super-acceleration and high time efficiency at 7 T for quantitative T(1) and diffusion imaging, while also retaining the capacity to perform quantitative T(2) and B(1) mapping. We demonstrate the super-acceleration of MESMERISED for whole-brain T(1) relaxometry with total acceleration factors up to 36 at 1.8 mm isotropic resolution, and up to 54 at 1.25 mm resolution qT(1) imaging, corresponding to a 6x and 9x speedup, respectively, compared to MB-only accelerated acquisitions. We then demonstrate highly efficient diffusion MRI with high b-values and long diffusion times in two separate cases. First, we show that super-accelerated multi-shell diffusion acquisitions with 370 whole-brain diffusion volumes over 8 b-value shells up to b = 7000 s/mm(2) can be generated at 2 mm isotropic in under 8 minutes, a data rate of almost a volume per second, or at 1.8 mm isotropic in under 11 minutes, achieving up to 3.4x speedup compared to MB-only. A comparison of b = 7000 s/mm(2) MESMERISED against standard MB pulsed gradient spin echo (PGSE) diffusion imaging shows 70% higher SNR efficiency and greater effectiveness in supporting complex diffusion signal modeling. Second, we demonstrate time-efficient sampling of different diffusion times with 1.8 mm isotropic diffusion data acquired at four diffusion times up to 290 ms, which supports both Diffusion Tensor Imaging (DTI) and Diffusion Kurtosis Imaging (DKI) at each diffusion time. Finally, we demonstrate how adding quantitative T(2) and B(1)(+) mapping to super-accelerated qT(1) and diffusion imaging enables efficient quantitative multi-contrast mapping with the same MESMERISED sequence and the same readout train. MESMERISED extends possibilities to efficiently probe T(1), T(2) and diffusion contrast for multi-component modeling of tissue microstructure.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Boonstra2021,

title = {Dedicated container for postmortem human brain ultra-high field magnetic resonance imaging.},

author = {Jackson Tyler Boonstra and Stijn Michielse and Alard Roebroeck and Yasin Temel and Ali Jahanshahi},

doi = {10.1016/j.neuroimage.2021.118010},

issn = {1095-9572 (Electronic)},

year  = {2021},

date = {2021-07-01},

journal = {NeuroImage},

volume = {235},

pages = {118010},

abstract = {BACKGROUND: The emerging field of ultra-high field MRI (UHF-MRI, 7 Tesla and higher) provides the opportunity to image human brains at a higher resolution and with higher signal-to-noise ratios compared to the more widely available 1.5 and 3T scanners. Scanning postmortem tissue additionally allows for greatly increased scan times and fewer movement issues leading to improvements in image quality. However, typical postmortem neuroimaging routines involve placing the tissue within plastic bags that leave room for susceptibility artifacts from tissue-air interfaces, inadequate submersion, and leakage issues. To address these challenges in postmortem imaging, a custom-built nonferromagnetic container was developed that allows whole brain hemispheres to be scanned at sub-millimeter resolution within typical head-coils. METHOD: The custom-built polymethylmethacrylaat container consists of a cylinder with a hemispheric side and a lid with valves on the adjacent side. This shape fits within common MR head-coils and allows whole hemispheres to be submerged and vacuum sealed within it reducing imaging artifacts that would otherwise arise at air-tissue boundaries. Two hemisphere samples were scanned on a Siemens 9.4T Magnetom MRI scanner. High resolution T2* weighted data was obtained with a custom 3D gradient echo (GRE) sequence and diffusion-weighted imaging (DWI) scans were obtained with a 3D kT-dSTEAM sequence along 48 directions. RESULTS: The custom-built container proved to submerge and contain tissue samples effectively and showed no interferences with MR scanning acquisition. The 3D GRE sequence provided high resolution isotropic T2* weighted data at 250 $mu$m which showed a clear visualization of gray and white matter structures. DWI scans allowed for dense reconstruction of structural white matter connections via tractography. CONCLUSION: Using this custom-built container worked towards achieving high quality MR images of postmortem brain material. This procedure can have advantages over traditional schemes including utilization of a standardized protocol and the reduced likelihood of leakage. This methodology could be adjusted and used to improve typical postmortem imaging routines.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{VanLanen2021,

title = {Ultra-high field magnetic resonance imaging in human epilepsy: A systematic review.},

author = {R H G J Lanen and A J Colon and C J Wiggins and M C Hoeberigs and G Hoogland and A Roebroeck and D Ivanov and B A Poser and R P W Rouhl and P A M Hofman and J F A Jansen and W Backes and K Rijkers and O E M G Schijns},

doi = {10.1016/j.nicl.2021.102602},

issn = {2213-1582 (Electronic)},

year  = {2021},

date = {2021-01-01},

journal = {NeuroImage. Clinical},

volume = {30},

pages = {102602},

abstract = {RATIONALE: Resective epilepsy surgery is an evidence-based curative treatment option for patients with drug-resistant focal epilepsy. The major preoperative predictor of a good surgical outcome is detection of an epileptogenic lesion by magnetic resonance imaging (MRI). Application of ultra-high field (UHF) MRI, i.e. field strengths ≥ 7 Tesla (T), may increase the sensitivity to detect such a lesion. METHODS: A keyword search strategy was submitted to Pubmed, EMBASE, Cochrane Database and clinicaltrials.gov to select studies on UHF MRI in patients with epilepsy. Follow-up study selection and data extraction were performed following PRISMA guidelines. We focused on I) diagnostic gain of UHF- over conventional MRI, II) concordance of MRI-detected lesion, seizure onset zone and surgical decision-making, and III) postoperative histopathological diagnosis and seizure outcome. RESULTS: Sixteen observational cohort studies, all using 7T MRI were included. Diagnostic gain of 7T over conventional MRI ranged from 8% to 67%, with a pooled gain of 31%. Novel techniques to visualize pathological processes in epilepsy and lesion detection are discussed. Seizure freedom was achieved in 73% of operated patients; no seizure outcome comparison was made between 7T MRI positive, 7T negative and 3T positive patients. 7T could influence surgical decision-making, with high concordance of lesion and seizure onset zone. Focal cortical dysplasia (54%), hippocampal sclerosis (12%) and gliosis (8.1%) were the most frequently diagnosed histopathological entities. SIGNIFICANCE: UHF MRI increases, yet variably, the sensitivity to detect an epileptogenic lesion, showing potential for use in clinical practice. It remains to be established whether this results in improved seizure outcome after surgical treatment. Prospective studies with larger cohorts of epilepsy patients, uniform scan and sequence protocols, and innovative post-processing technology are equally important as further increasing field strengths. Besides technical ameliorations, improved correlation of imaging features with clinical semiology, histopathology and clinical outcome has to be established.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hildebrand2020,

title = {hFRUIT: An optimized agent for optical clearing of DiI-stained adult human brain tissue.},

author = {Sven Hildebrand and Anna Schueth and Klaus Wangenheim and Christian Mattheyer and Francesco Pampaloni and Hansjürgen Bratzke and Alard F Roebroeck and Ralf A W Galuske},

doi = {10.1038/s41598-020-66999-3},

issn = {2045-2322 (Electronic)},

year  = {2020},

date = {2020-06-01},

journal = {Scientific reports},

volume = {10},

number = {1},

pages = {9950},

abstract = {Here, we describe a new immersion-based clearing method suitable for optical clearing of thick adult human brain samples while preserving its lipids and lipophilic labels such as 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI). This clearing procedure is simple, easy to implement, and allowed for clearing of 5 mm thick human brain tissue samples within 12 days. Furthermore, we show for the first time the advantageous effect of the Periodate-Lysine-Paraformaldehyde (PLP) fixation as compared to the more commonly used 4% paraformaldehyde (PFA) on clearing performance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Franssen2020,

title = {Power of mind: Attentional focus rather than palatability dominates neural responding to visual food stimuli in females with overweight.},

author = {Sieske Franssen and Anita Jansen and Job Hurk and Alard Roebroeck and Anne Roefs},

doi = {10.1016/j.appet.2020.104609},

issn = {1095-8304 (Electronic)},

year  = {2020},

date = {2020-05-01},

journal = {Appetite},

volume = {148},

pages = {104609},

abstract = {Research investigating neural responses to visual food stimuli has produced inconsistent results. Crucially, high-caloric palatable foods have a double-sided nature - they are often craved but are also considered unhealthy - which may have contributed to the inconsistency in the literature. Taking this double-sided nature into account in the current study, neural responses to individually tailored palatable and unpalatable high caloric food stimuli were measured, while participants' (females with overweight: n = 23) attentional focus was manipulated to be either hedonic or neutral. Notably, results showed that the level of neural activity was not significantly different for palatable than for unpalatable food stimuli. Instead, independent of food palatability, several brain regions (including regions in the mesocorticolimbic system) responded more strongly when attentional focus was hedonic than when neutral (p < 0.05, cluster-based FWE corrected). Multivariate analyses showed that food palatability could be decoded from multi-voxel patterns of neural activity (p < 0.05, FDR corrected), mostly with a hedonic attentional focus. These findings illustrate that the level of neural activity might not be proportionate to the palatability of foods, but that food palatability can be decoded from multi-voxel patterns of neural activity. Moreover, they underline the importance of considering attentional focus when measuring food-related neural responses.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gonzalez-Escamilla2020,

title = {Gray matter network reorganization in multiple sclerosis from 7-Tesla and 3-Tesla MRI data.},

author = {Gabriel Gonzalez-Escamilla and Dumitru Ciolac and Silvia De Santis and Angela Radetz and Vinzenz Fleischer and Amgad Droby and Alard Roebroeck and Sven G Meuth and Muthuraman Muthuraman and Sergiu Groppa},

doi = {10.1002/acn3.51029},

issn = {2328-9503 (Electronic)},

year  = {2020},

date = {2020-04-01},

journal = {Annals of clinical and translational neurology},

volume = {7},

number = {4},

pages = {543--553},

abstract = {OBJECTIVE: The objective of this study was to determine the ability of 7T-MRI for characterizing brain tissue integrity in early relapsing-remitting MS patients compared to conventional 3T-MRI and to investigate whether 7T-MRI improves the performance for detecting cortical gray matter neurodegeneration and its associated network reorganization dynamics. METHODS: Seven early relapsing-remitting MS patients and seven healthy individuals received MRI at 7T and 3T, whereas 30 and 40 healthy controls underwent separate 3T- and 7T-MRI sessions, respectively. Surface-based cortical thickness (CT) and gray-to-white contrast (GWc) measures were used to model morphometric networks, analyzed with graph theory by means of modularity, clustering coefficient, path length, and small-worldness. RESULTS: 7T-MRI had lower CT and higher GWc compared to 3T-MRI in MS. CT and GWc measures robustly differentiated MS from controls at 3T-MRI. 7T- and 3T-MRI showed high regional correspondence for CT (r = 0.72},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fritz2019,

title = {Ultra-high resolution and multi-shell diffusion MRI of intact ex vivo human brains using k(T)-dSTEAM at 9.4T.},

author = {F J Fritz and S Sengupta and R L Harms and D H Tse and B A Poser and A Roebroeck},

doi = {10.1016/j.neuroimage.2019.116087},

issn = {1095-9572 (Electronic)},

year  = {2019},

date = {2019-11-01},

journal = {NeuroImage},

volume = {202},

pages = {116087},

abstract = {Diffusion MRI (dMRI) in ex vivo human brain specimens is an important research tool for neuroanatomical investigations and the validation of dMRI techniques. Many ex vivo dMRI applications have benefited from very high dMRI resolutions achievable on small-bore preclinical or animal MRI scanners for small tissue samples. However, the investigation of entire human brains post mortem provides the important context of entire white matter (WM) network systems and entire gray matter (GM) areas connected through these systems. The investigation of intact ex vivo human brains in large bore systems creates challenges due to the limited gradient performance and transmit radio-frequency (B(1)+) inhomogeneities, specially at ultra-high field (UHF, 7T and higher). To overcome these issues, it is necessary to tailor ex vivo diffusion-weighted sequences specifically for high resolution and high diffusion-weighting. Here, we present k(T)-dSTEAM, which achieves B(1)+ homogenization across whole human brain specimens using parallel transmit (pTx) on a 9.4T MR system. We use k(T)-dSTEAM to obtain multi-shell high b-value and high resolution diffusion-weighted data in ex vivo whole human brains. Isotropic whole brain data can be acquired at high b-value (6000-8000 s/mm(2)) at high resolution (1000 $mu$m) and at moderate b-value (3000 s/mm(2)) at ultra-high isotropic resolution (400 $mu$m). As an illustration of the advantages of the ultra-high resolution, tractography across the WM/GM border shows less of the unwanted gyral crown bias, and more high-curvature paths connecting the sulcal wall than at lower resolution. The k(T)-dSTEAM also allows for acquisition of T(1) and T(2) weighted images suitable for estimating quantitative T(1) and T(2) maps. Finally, multi-shell analysis of k(T)-dSTEAM data at variable mixing time (TM) is shown as an approach for ex vivo data analysis which is adapted to the strengths of STEAM diffusion-weighting. Here, we use this gain for multi-orientation modelling and crossing-fiber tractography. We show that multi-shell data allows superior multiple orientation tractography of known crossing fiber structures in the brain stem.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Voigt2019,

title = {The mesoSPIM initiative: open-source light-sheet microscopes for imaging cleared tissue.},

author = {Fabian F Voigt and Daniel Kirschenbaum and Evgenia Platonova and Stéphane Pagès and Robert A A Campbell and Rahel Kastli and Martina Schaettin and Ladan Egolf and Alexander Bourg and Philipp Bethge and Karen Haenraets and Noémie Frézel and Thomas Topilko and Paola Perin and Daniel Hillier and Sven Hildebrand and Anna Schueth and Alard Roebroeck and Botond Roska and Esther T Stoeckli and Roberto Pizzala and Nicolas Renier and Hanns Ulrich Zeilhofer and Theofanis Karayannis and Urs Ziegler and Laura Batti and Anthony Holtmaat and Christian Lüscher and Adriano Aguzzi and Fritjof Helmchen},

doi = {10.1038/s41592-019-0554-0},

issn = {1548-7105 (Electronic)},

year  = {2019},

date = {2019-11-01},

journal = {Nature methods},

volume = {16},

number = {11},

pages = {1105--1108},

abstract = {Light-sheet microscopy is an ideal technique for imaging large cleared samples; however, the community is still lacking instruments capable of producing volumetric images of centimeter-sized cleared samples with near-isotropic resolution within minutes. Here, we introduce the mesoscale selective plane-illumination microscopy initiative, an open-hardware project for building and operating a light-sheet microscope that addresses these challenges and is compatible with any type of cleared or expanded sample ( www.mesospim.org ).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hildebrand2019,

title = {Scalable Labeling for Cytoarchitectonic Characterization of Large Optically Cleared Human Neocortex Samples.},

author = {Sven Hildebrand and Anna Schueth and Andreas Herrler and Ralf Galuske and Alard Roebroeck},

doi = {10.1038/s41598-019-47336-9},

issn = {2045-2322 (Electronic)},

year  = {2019},

date = {2019-07-01},

journal = {Scientific reports},

volume = {9},

number = {1},

pages = {10880},

abstract = {Optical clearing techniques and light sheet microscopy have transformed fluorescent imaging of rodent brains, and have provided a crucial alternative to traditional confocal or bright field techniques for thin sections. However, clearing and labeling human brain tissue through all cortical layers and significant portions of a cortical area, has so far remained extremely challenging, especially for formalin fixed adult cortical tissue. Here, we present MASH (Multiscale Architectonic Staining of Human cortex): a simple, fast and low-cost cytoarchitectonic labeling approach for optically cleared human cortex samples, which can be applied to large (up to 5 mm thick) formalin fixed adult brain samples. A suite of small-molecule fluorescent nuclear and cytoplasmic dye protocols in combination with new refractive index matching solutions allows deep volume imaging. This greatly reduces time and cost of imaging cytoarchitecture in thick samples and enables classification of cytoarchitectonic layers over the full cortical depth. We demonstrate application of MASH to large archival samples of human visual areas, characterizing cortical architecture in 3D from the scale of cortical areas to that of single cells. In combination with scalable light sheet imaging and data analysis, MASH could open the door to investigation of large human cortical systems at cellular resolution and in the context of their complex 3-dimensional geometry.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Roebroeck2019,

title = {Ex vivo diffusion MRI of the human brain: Technical challenges and recent advances.},

author = {Alard Roebroeck and Karla L Miller and Manisha Aggarwal},

doi = {10.1002/nbm.3941},

issn = {1099-1492 (Electronic)},

year  = {2019},

date = {2019-04-01},

journal = {NMR in biomedicine},

volume = {32},

number = {4},

pages = {e3941},

abstract = {This review discusses ex vivo diffusion magnetic resonance imaging (dMRI) as an important research tool for neuroanatomical investigations and the validation of in vivo dMRI techniques, with a focus on the human brain. We review the challenges posed by the properties of post-mortem tissue, and discuss state-of-the-art tissue preparation methods and recent advances in pulse sequences and acquisition techniques to tackle these. We then review recent ex vivo dMRI studies of the human brain, highlighting the validation of white matter orientation estimates and the atlasing and mapping of large subcortical structures. We also give particular emphasis to the delineation of layered gray matter structure with ex vivo dMRI, as this application illustrates the strength of its mesoscale resolution over large fields of view. We end with a discussion and outlook on future and potential directions of the field.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{DeSantis2019,

title = {Characterizing Microstructural Tissue Properties in Multiple Sclerosis with Diffusion MRI at 7 T and 3 T: The Impact of the Experimental Design.},

author = {Silvia De Santis and Matteo Bastiani and Amgad Droby and Pierre Kolber and Frauke Zipp and Eberhard Pracht and Tony Stoecker and Sergiu Groppa and Alard Roebroeck},

doi = {10.1016/j.neuroscience.2018.03.048},

issn = {1873-7544 (Electronic)},

year  = {2019},

date = {2019-04-01},

journal = {Neuroscience},

volume = {403},

pages = {17--26},

abstract = {The recent introduction of advanced magnetic resonance (MR) imaging techniques to characterize focal and global degeneration in multiple sclerosis (MS), like the Composite Hindered and Restricted Model of Diffusion, or CHARMED, diffusional kurtosis imaging (DKI) and Neurite Orientation Dispersion and Density Imaging (NODDI) made available new tools to image axonal pathology non-invasively in vivo. These methods already showed greater sensitivity and specificity compared to conventional diffusion tensor-based metrics (e.g., fractional anisotropy), overcoming some of its limitations. While previous studies uncovered global and focal axonal degeneration in MS patients compared to healthy controls, here our aim is to investigate and compare different diffusion MRI acquisition protocols in their ability to highlight microstructural differences between MS and control tissue over several much used models. For comparison, we contrasted the ability of fractional anisotropy measurements to uncover differences between lesion, normal-appearing white matter (WM), gray matter and healthy tissue under the same imaging protocols. We show that: (1) focal and diffuse differences in several microstructural parameters are observed under clinical settings; (2) advanced models (CHARMED, DKI and NODDI) have increased specificity and sensitivity to neurodegeneration when compared to fractional anisotropy measurements; and (3) both high (3 T) and ultra-high fields (7 T) are viable options for imaging tissue change in MS lesions and normal appearing WM, while higher b-values are less beneficial under the tested short-time (10 min acquisition) conditions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Jacobs2018,

title = {Curvilinear locus coeruleus functional connectivity trajectories over the adult lifespan: a 7T MRI study.},

author = {Heidi I L Jacobs and Lisa Müller-Ehrenberg and Nikos Priovoulos and Alard Roebroeck},

doi = {10.1016/j.neurobiolaging.2018.05.021},

issn = {1558-1497 (Electronic)},

year  = {2018},

date = {2018-09-01},

journal = {Neurobiology of aging},

volume = {69},

pages = {167--176},

abstract = {The locus coeruleus (LC) plays a crucial role in modulating several higher order cognitive functions via its widespread projections to the entire brain. We set out to investigate the hypothesis that LC functional connectivity (FC) may fluctuate nonlinearly with age and explored its relation to memory function. To that end, 49 cognitively healthy individuals (19-74 years) underwent ultra high-resolution 7T resting-state functional magnetic resonance imaging and cognitive testing. FC patterns from the LC to regions of the isodendritic core network and cortical regions were examined using region of interest-to-region of interest analyses. Curvilinear patterns with age were observed for FC between the left LC and cortical regions and the nucleus basalis of Meynert. A linear negative association was observed between age and LC-FC and ventral tegmental area. Higher levels of FC between the LC and nucleus basalis of Meynert or ventral tegmental area were associated with lower memory performance from age of 40 years onward. Thus, different LC-FC patterns early in life can signal subtle memory deficits. Furthermore, these results highlight the importance of intact interactions between neurotransmitter systems for optimal cognitive aging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pracht2018,

title = {SAR and scan-time optimized 3D whole-brain double inversion recovery imaging at 7T.},

author = {Eberhard D Pracht and Thorsten Feiweier and Philipp Ehses and Daniel Brenner and Alard Roebroeck and Bernd Weber and Tony Stöcker},

doi = {10.1002/mrm.26913},

issn = {1522-2594 (Electronic)},

year  = {2018},

date = {2018-05-01},

journal = {Magnetic resonance in medicine},

volume = {79},

number = {5},

pages = {2620--2628},

abstract = {PURPOSE: The aim of this project was to implement an ultra-high field (UHF) optimized double inversion recovery (DIR) sequence for gray matter (GM) imaging, enabling whole brain coverage in short acquisition times ( ≈5 min, image resolution 1 mm(3) ). METHODS: A 3D variable flip angle DIR turbo spin echo (TSE) sequence was optimized for UHF application. We implemented an improved, fast, and specific absorption rate (SAR) efficient TSE imaging module, utilizing improved reordering. The DIR preparation was tailored to UHF application. Additionally, fat artifacts were minimized by employing water excitation instead of fat saturation. RESULTS: GM images, covering the whole brain, were acquired in 7 min scan time at 1 mm isotropic resolution. SAR issues were overcome by using a dedicated flip angle calculation considering SAR and SNR efficiency. Furthermore, UHF related artifacts were minimized. CONCLUSION: The suggested sequence is suitable to generate GM images with whole-brain coverage at UHF. Due to the short total acquisition times and overall robustness, this approach can potentially enable DIR application in a routine setting and enhance lesion detection in neurological diseases. Magn Reson Med 79:2620-2628, 2018. textcopyright 2017 International Society for Magnetic Resonance in Medicine.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sengupta2018,

title = {High resolution anatomical and quantitative MRI of the entire human occipital lobe ex vivo at 9.4T.},

author = {S Sengupta and F J Fritz and R L Harms and S Hildebrand and D H Y Tse and B A Poser and R Goebel and A Roebroeck},

doi = {10.1016/j.neuroimage.2017.03.039},

issn = {1095-9572 (Electronic)},

year  = {2018},

date = {2018-03-01},

journal = {NeuroImage},

volume = {168},

pages = {162--171},

abstract = {Several magnetic resonance imaging (MRI) contrasts are sensitive to myelin content in gray matter in vivo which has ignited ambitions of MRI-based in vivo cortical histology. Ultra-high field (UHF) MRI, at fields of 7T and beyond, is crucial to provide the resolution and contrast needed to sample contrasts over the depth of the cortex and get closer to layer resolved imaging. Ex vivo MRI of human post mortem samples is an important stepping stone to investigate MRI contrast in the cortex, validate it against histology techniques applied in situ to the same tissue, and investigate the resolutions needed to translate ex vivo findings to in vivo UHF MRI. Here, we investigate key technology to extend such UHF studies to large human brain samples while maintaining high resolution, which allows investigation of the layered architecture of several cortical areas over their entire 3D extent and their complete borders where architecture changes. A 16 channel cylindrical phased array radiofrequency (RF) receive coil was constructed to image a large post mortem occipital lobe sample ($sim$80×80×80mm(3)) in a wide-bore 9.4T human scanner with the aim of achieving high-resolution anatomical and quantitative MR images. Compared with a human head coil at 9.4T, the maximum Signal-to-Noise ratio (SNR) was increased by a factor of about five in the peripheral cortex. Although the transmit profile with a circularly polarized transmit mode at 9.4T is relatively inhomogeneous over the large sample, this challenge was successfully resolved with parallel transmit using the kT-points method. Using this setup, we achieved 60$mu$m anatomical images for the entire occipital lobe showing increased spatial definition of cortical details compared to lower resolutions. In addition, we were able to achieve sufficient control over SNR, B(0) and B(1) homogeneity and multi-contrast sampling to perform quantitative T(2)* mapping over the same volume at 200$mu$m. Markov Chain Monte Carlo sampling provided maximum posterior estimates of quantitative T(2)* and their uncertainty, allowing delineation of the stria of Gennari over the entire length and width of the calcarine sulcus. We discuss how custom RF receive coil arrays built to specific large post mortem sample sizes can provide a platform for UHF cortical layer-specific quantitative MRI over large fields of view.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Plantinga2018,

title = {Individualized parcellation of the subthalamic nucleus in patients with Parkinson's disease with 7T MRI.},

author = {Birgit R Plantinga and Yasin Temel and Yuval Duchin and Kâmil Uludağ and Rémi Patriat and Alard Roebroeck and Mark Kuijf and Ali Jahanshahi and Bart Ter Haar Romenij and Jerrold Vitek and Noam Harel},

doi = {10.1016/j.neuroimage.2016.09.023},

issn = {1095-9572 (Electronic)},

year  = {2018},

date = {2018-03-01},

journal = {NeuroImage},

volume = {168},

pages = {403--411},

abstract = {Deep brain stimulation of the subthalamic nucleus (STN) is a widely performed surgical treatment for patients with Parkinson's disease. The goal of the surgery is to place an electrode centered in the motor region of the STN while lowering the effects of electrical stimulation on the non-motor regions. However, distinguishing the motor region from the neighboring associative and limbic areas in individual patients using imaging modalities was until recently difficult to obtain in vivo. Here, using ultra-high field MR imaging, we have performed a dissection of the subdivisions of the STN of individual Parkinson's disease patients. We have acquired 7T diffusion-weighted images of seventeen patients with Parkinson's disease scheduled for deep brain stimulation surgery. Using a structural connectivity-based parcellation protocol, the STN's connections to the motor, limbic, and associative cortical areas were used to map the individual subdivisions of the nucleus. A reproducible patient-specific parcellation of the STN into a posterolateral motor and gradually overlapping central associative area was found in all STNs, taking up on average 55.3% and 55.6% of the total nucleus volume. The limbic area was found in the anteromedial part of the nucleus. Our results suggest that 7T MR imaging may facilitate individualized and highly specific planning of deep brain stimulation surgery of the STN.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Harms2018,

title = {Robust and Fast Markov Chain Monte Carlo Sampling of Diffusion MRI Microstructure Models.},

author = {Robbert L Harms and Alard Roebroeck},

doi = {10.3389/fninf.2018.00097},

issn = {1662-5196 (Print)},

year  = {2018},

date = {2018-01-01},

journal = {Frontiers in neuroinformatics},

volume = {12},

pages = {97},

abstract = {In diffusion MRI analysis, advances in biophysical multi-compartment modeling have gained popularity over the conventional Diffusion Tensor Imaging (DTI), because they can obtain a greater specificity in relating the dMRI signal to underlying cellular microstructure. Biophysical multi-compartment models require a parameter estimation, typically performed using either the Maximum Likelihood Estimation (MLE) or the Markov Chain Monte Carlo (MCMC) sampling. Whereas, the MLE provides only a point estimate of the fitted model parameters, the MCMC recovers the entire posterior distribution of the model parameters given in the data, providing additional information such as parameter uncertainty and correlations. MCMC sampling is currently not routinely applied in dMRI microstructure modeling, as it requires adjustment and tuning, specific to each model, particularly in the choice of proposal distributions, burn-in length, thinning, and the number of samples to store. In addition, sampling often takes at least an order of magnitude, more time than non-linear optimization. Here we investigate the performance of the MCMC algorithm variations over multiple popular diffusion microstructure models, to examine whether a single, well performing variation could be applied efficiently and robustly to many models. Using an efficient GPU-based implementation, we showed that run times can be removed as a prohibitive constraint for the sampling of diffusion multi-compartment models. Using this implementation, we investigated the effectiveness of different adaptive MCMC algorithms, burn-in, initialization, and thinning. Finally we applied the theory of the Effective Sample Size, to the diffusion multi-compartment models, as a way of determining a relatively general target for the number of samples needed to characterize parameter distributions for different models and data sets. We conclude that adaptive Metropolis methods increase MCMC performance and select the Adaptive Metropolis-Within-Gibbs (AMWG) algorithm as the primary method. We furthermore advise to initialize the sampling with an MLE point estimate, in which case 100 to 200 samples are sufficient as a burn-in. Finally, we advise against thinning in most use-cases and as a relatively general target for the number of samples, we recommend a multivariate Effective Sample Size of 2,200.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tobisch2018,

title = {Compressed Sensing Diffusion Spectrum Imaging for Accelerated Diffusion Microstructure MRI in Long-Term Population Imaging.},

author = {Alexandra Tobisch and Rüdiger Stirnberg and Robbert L Harms and Thomas Schultz and Alard Roebroeck and Monique M B Breteler and Tony Stöcker},

doi = {10.3389/fnins.2018.00650},

issn = {1662-4548 (Print)},

year  = {2018},

date = {2018-01-01},

journal = {Frontiers in neuroscience},

volume = {12},

pages = {650},

abstract = {Mapping non-invasively the complex microstructural architecture of the living human brain, diffusion magnetic resonance imaging (dMRI) is one of the core imaging modalities in current population studies. For the application in longitudinal population imaging, the dMRI protocol should deliver reliable data with maximum potential for future analysis. With the recent introduction of novel MRI hardware, advanced dMRI acquisition strategies can be applied within reasonable scan time. In this work we conducted a pilot study based on the requirements for high resolution dMRI in a long-term and high throughput population study. The key question was: can diffusion spectrum imaging accelerated by compressed sensing theory (CS-DSI) be used as an advanced imaging protocol for microstructure dMRI in a long-term population imaging study? As a minimum requirement we expected a high level of agreement of several diffusion metrics derived from both CS-DSI and a 3-shell high angular resolution diffusion imaging (HARDI) acquisition, an established imaging strategy used in other population studies. A wide spectrum of state-of-the-art diffusion processing and analysis techniques was applied to the pilot study data including quantitative diffusion and microstructural parameter mapping, fiber orientation estimation and white matter fiber tracking. When considering diffusion weighted images up to the same maximum diffusion weighting for both protocols, group analysis across 20 subjects indicates that CS-DSI performs comparable to 3-shell HARDI in the estimation of diffusion and microstructural parameters. Further, both protocols provide similar results in the estimation of fiber orientations and for local fiber tracking. CS-DSI provides high radial resolution while maintaining high angular resolution and it is well-suited for analysis strategies that require high b-value acquisitions, such as CHARMED modeling and biomarkers from the diffusion propagator.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Harms2017,

title = {Robust and fast nonlinear optimization of diffusion MRI microstructure models.},

author = {R L Harms and F J Fritz and A Tobisch and R Goebel and A Roebroeck},

doi = {10.1016/j.neuroimage.2017.04.064},

issn = {1095-9572 (Electronic)},

year  = {2017},

date = {2017-07-01},

journal = {NeuroImage},

volume = {155},

pages = {82--96},

abstract = {Advances in biophysical multi-compartment modeling for diffusion MRI (dMRI) have gained popularity because of greater specificity than DTI in relating the dMRI signal to underlying cellular microstructure. A large range of these diffusion microstructure models have been developed and each of the popular models comes with its own, often different, optimization algorithm, noise model and initialization strategy to estimate its parameter maps. Since data fit, accuracy and precision is hard to verify, this creates additional challenges to comparability and generalization of results from diffusion microstructure models. In addition, non-linear optimization is computationally expensive leading to very long run times, which can be prohibitive in large group or population studies. In this technical note we investigate the performance of several optimization algorithms and initialization strategies over a few of the most popular diffusion microstructure models, including NODDI and CHARMED. We evaluate whether a single well performing optimization approach exists that could be applied to many models and would equate both run time and fit aspects. All models, algorithms and strategies were implemented on the Graphics Processing Unit (GPU) to remove run time constraints, with which we achieve whole brain dataset fits in seconds to minutes. We then evaluated fit, accuracy, precision and run time for different models of differing complexity against three common optimization algorithms and three parameter initialization strategies. Variability of the achieved quality of fit in actual data was evaluated on ten subjects of each of two population studies with a different acquisition protocol. We find that optimization algorithms and multi-step optimization approaches have a considerable influence on performance and stability over subjects and over acquisition protocols. The gradient-free Powell conjugate-direction algorithm was found to outperform other common algorithms in terms of run time, fit, accuracy and precision. Parameter initialization approaches were found to be relevant especially for more complex models, such as those involving several fiber orientations per voxel. For these, a fitting cascade initializing or fixing parameter values in a later optimization step from simpler models in an earlier optimization step further improved run time, fit, accuracy and precision compared to a single step fit. This establishes and makes available standards by which robust fit and accuracy can be achieved in shorter run times. This is especially relevant for the use of diffusion microstructure modeling in large group or population studies and in combining microstructure parameter maps with tractography results.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Havlicek2017a,

title = {On the importance of modeling fMRI transients when estimating effective connectivity: A dynamic causal modeling study using ASL data.},

author = {Martin Havlicek and Alard Roebroeck and Karl J Friston and Anna Gardumi and Dimo Ivanov and Kamil Uludag},

doi = {10.1016/j.neuroimage.2017.03.017},

issn = {1095-9572 (Electronic)},

year  = {2017},

date = {2017-07-01},

journal = {NeuroImage},

volume = {155},

pages = {217--233},

abstract = {Effective connectivity is commonly assessed using blood oxygenation level-dependent (BOLD) signals. In (Havlicek et al., 2015), we presented a novel, physiologically informed dynamic causal model (P-DCM) that extends current generative models. We demonstrated the improvements afforded by P-DCM in terms of the ability to model commonly observed neuronal and vascular transients in single regions. Here, we assess the ability of the novel and previous DCM variants to estimate effective connectivity among a network of five ROIs driven by a visuo-motor task. We demonstrate that connectivity estimates depend sensitively on the DCM used, due to differences in the modeling of hemodynamic response transients; such as the post-stimulus undershoot or adaptation during stimulation. In addition, using a novel DCM for arterial spin labeling (ASL) fMRI that measures BOLD and CBF signals simultaneously, we confirmed our findings (by using the BOLD data alone and in conjunction with CBF). We show that P-DCM provides better estimates of effective connectivity, regardless of whether it is applied to BOLD data alone or to ASL time-series, and that all new aspects of P-DCM (i.e. neuronal, neurovascular, hemodynamic components) constitute an improvement compared to those in the previous DCM variants. In summary, (i) accurate modeling of fMRI response transients is crucial to obtain valid effective connectivity estimates and (ii) any additional hemodynamic data, such as provided by ASL, increases the ability to disambiguate neuronal and vascular effects present in the BOLD signal.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kolber2017,

title = {A "kissing lesion": In-vivo 7T evidence of meningeal inflammation in early multiple sclerosis.},

author = {Pierre Kolber and Amgad Droby and Alard Roebroeck and Rainer Goebel and Vinzenz Fleischer and Sergiu Groppa and Frauke Zipp},

doi = {10.1177/1352458516683267},

issn = {1477-0970 (Electronic)},

year  = {2017},

date = {2017-07-01},

journal = {Multiple sclerosis (Houndmills, Basingstoke, England)},

volume = {23},

number = {8},

pages = {1167--1169},

abstract = {BACKGROUND: The role of cortical lesions (CLs) in disease progression and clinical deficits is increasingly recognized in multiple sclerosis (MS); however the origin of CLs in MS still remains unclear. OBJECTIVE: Here, we report a para-sulcal CL detected two years after diagnosis in a relapsing-remitting MS (RRMS) patient without manifestation of clinical deficit. METHODS: Ultra-high field (7T) MR imaging using magnetization-prepared 2 rapid acquisition gradient echoes (MP2RAGE) sequence was performed. RESULTS: A para-sulcal CL was detected which showed hypointense rim and iso- to hyperintense core. This was detected in the proximity of the leptomeninges in the left precentral gyrus extending to the adjacent postcentral gyrus. CONCLUSION: This finding indicates that inflammatory infiltration into the cortex through the meninges underlies cortical pathology already in the early stage of disease and in mild disease course.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Havlicek2017,

title = {Determining Excitatory and Inhibitory Neuronal Activity from Multimodal fMRI Data Using a Generative Hemodynamic Model.},

author = {Martin Havlicek and Dimo Ivanov and Alard Roebroeck and Kamil Uludağ},

doi = {10.3389/fnins.2017.00616},

issn = {1662-4548 (Print)},

year  = {2017},

date = {2017-01-01},

journal = {Frontiers in neuroscience},

volume = {11},

pages = {616},

abstract = {Hemodynamic responses, in general, and the blood oxygenation level-dependent (BOLD) fMRI signal, in particular, provide an indirect measure of neuronal activity. There is strong evidence that the BOLD response correlates well with post-synaptic changes, induced by changes in the excitatory and inhibitory (E-I) balance between active neuronal populations. Typical BOLD responses exhibit transients, such as the early-overshoot and post-stimulus undershoot, that can be linked to transients in neuronal activity, but they can also result from vascular uncoupling between cerebral blood flow (CBF) and venous cerebral blood volume (venous CBV). Recently, we have proposed a novel generative hemodynamic model of the BOLD signal within the dynamic causal modeling framework, inspired by physiological observations, called P-DCM (Havlicek et al., 2015). We demonstrated the generative model's ability to more accurately model commonly observed neuronal and vascular transients in single regions but also effective connectivity between multiple brain areas (Havlicek et al., 2017b). In this paper, we additionally demonstrate the versatility of the generative model to jointly explain dynamic relationships between neuronal and hemodynamic physiological variables underlying the BOLD signal using multi-modal data. For this purpose, we utilized three distinct data-sets of experimentally induced responses in the primary visual areas measured in human, cat, and monkey brain, respectively: (1) CBF and BOLD responses; (2) CBF, total CBV, and BOLD responses (Jin and Kim, 2008); and (3) positive and negative neuronal and BOLD responses (Shmuel et al., 2006). By fitting the generative model to the three multi-modal experimental data-sets, we showed that the presence or absence of dynamic features in the BOLD signal is not an unambiguous indication of presence or absence of those features on the neuronal level. Nevertheless, the generative model that takes into account the dynamics of the physiological mechanisms underlying the BOLD response allowed dissociating neuronal from vascular transients and deducing excitatory and inhibitory neuronal activity time-courses from BOLD data alone and from multi-modal data.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Domen2017,

title = {Differential Time Course of Microstructural White Matter in Patients With Psychotic Disorder and Individuals at Risk: A 3-Year Follow-up Study.},

author = {Patrick Domen and Sanne Peeters and Stijn Michielse and Ed Gronenschild and Wolfgang Viechtbauer and Alard Roebroeck and Jim Os and Machteld Marcelis},

doi = {10.1093/schbul/sbw061},

issn = {1745-1701 (Electronic)},

year  = {2017},

date = {2017-01-01},

journal = {Schizophrenia bulletin},

volume = {43},

number = {1},

pages = {160--170},

institution = {for Genetic Risk and Outcome of Psychosis (G.R.O.U.P.)},

abstract = {BACKGROUND: Although widespread reduced white matter (WM) integrity is a consistent finding in cross-sectional diffusion tensor imaging (DTI) studies of schizophrenia, little is known about the course of these alterations. This study examined to what degree microstructural WM alterations display differential trajectories over time as a function of level of psychosis liability. METHODS: Two DTI scans with a 3-year time interval were acquired from 159 participants (55 patients with a psychotic disorder, 55 nonpsychotic siblings and 49 healthy controls) and processed with tract-based spatial statistics. The mean fractional anisotropy (FA) change over time was calculated. Main effects of group, as well as group × region interactions in the model of FA change were examined with multilevel (mixed-effects) models. RESULTS: Siblings revealed a significant mean FA decrease over time compared to controls (B = -0.004},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{DeSantis2016,

title = {T1 relaxometry of crossing fibres in the human brain.},

author = {Silvia De Santis and Yaniv Assaf and Ben Jeurissen and Derek K Jones and Alard Roebroeck},

doi = {10.1016/j.neuroimage.2016.07.037},

issn = {1095-9572 (Electronic)},

year  = {2016},

date = {2016-11-01},

journal = {NeuroImage},

volume = {141},

pages = {133--142},

abstract = {A comprehensive tract-based characterisation of white matter should include the ability to quantify myelin and axonal attributes irrespective of the complexity of fibre organisation within the voxel. Recently, a new experimental framework that combines inversion recovery and diffusion MRI, called inversion recovery diffusion tensor imaging (IR-DTI), was introduced and applied in an animal study. IR-DTI provides the ability to assign to each unique fibre population within a voxel a specific value of the longitudinal relaxation time, T1, which is a proxy for myelin content. Here, we apply the IR-DTI approach to the human brain in vivo on 7 healthy subjects for the first time. We demonstrate that the approach is able to measure differential tract properties in crossing fibre areas, reflecting the different myelination of tracts. We also show that tract-specific T1 has less inter-subject variability compared to conventional T1 in areas of crossing fibres, suggesting increased specificity to distinct fibre populations. Finally we show in simulations that changes in myelination selectively affecting one fibre bundle in crossing fibre areas can potentially be detected earlier using IR-DTI.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{DeSantis2016a,

title = {Including diffusion time dependence in the extra-axonal space improves in vivo estimates of axonal diameter and density in human white matter.},

author = {Silvia De Santis and Derek K Jones and Alard Roebroeck},

doi = {10.1016/j.neuroimage.2016.01.047},

issn = {1095-9572 (Electronic)},

year  = {2016},

date = {2016-04-01},

journal = {NeuroImage},

volume = {130},

pages = {91--103},

abstract = {Axonal density and diameter are two fundamental properties of brain white matter. Recently, advanced diffusion MRI techniques have made these two parameters accessible in vivo. However, the techniques available to estimate such parameters are still under development. For example, current methods to map axonal diameters capture relative trends over different structures, but consistently over-estimate absolute diameters. Axonal density estimates are more accessible experimentally, but different modeling approaches exist and the impact of the experimental parameters has not been thoroughly quantified, potentially leading to incompatibility of results obtained in different studies using different techniques. Here, we characterise the impact of diffusion time on axonal density and diameter estimates using Monte Carlo simulations and STEAM diffusion MRI at 7 T on 9 healthy volunteers. We show that axonal density and diameter estimates strongly depend on diffusion time, with diameters almost invariably overestimated and density both over and underestimated for some commonly used models. Crucially, we also demonstrate that these biases are reduced when the model accounts for diffusion time dependency in the extra-axonal space. For axonal density estimates, both upward and downward bias in different situations are removed by modeling extra-axonal time-dependence, showing increased accuracy in these estimates. For axonal diameter estimates, we report increased accuracy in ground truth simulations and axonal diameter estimates decreased away from high values given by earlier models and towards known values in the human corpus callosum when modeling extra-axonal time-dependence. Axonal diameter feasibility under both advanced and clinical settings is discussed in the light of the proposed advances.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Timmers2016,

title = {Assessing Microstructural Substrates of White Matter Abnormalities: A Comparative Study Using DTI and NODDI.},

author = {Inge Timmers and Alard Roebroeck and Matteo Bastiani and Bernadette Jansma and Estela Rubio-Gozalbo and Hui Zhang},

doi = {10.1371/journal.pone.0167884},

issn = {1932-6203 (Electronic)},

year  = {2016},

date = {2016-01-01},

journal = {PloS one},

volume = {11},

number = {12},

pages = {e0167884},

abstract = {Neurite orientation dispersion and density imaging (NODDI) enables more specific characterization of tissue microstructure by estimating neurite density (NDI) and orientation dispersion (ODI), two key contributors to fractional anisotropy (FA). The present work compared NODDI- with diffusion tensor imaging (DTI)-derived indices for investigating white matter abnormalities in a clinical sample. We assessed the added value of NODDI parameters over FA, by contrasting group differences identified by both models. Diffusion-weighted images with multiple shells were acquired in a group of 8 healthy controls and 8 patients with an inherited metabolic disease. Both standard DTI and NODDI analyses were performed. Tract based spatial statistics (TBSS) was used for group inferences, after which overlap and unique contributions across different parameters were evaluated. Results showed that group differences in NDI and ODI were complementary, and together could explain much of the FA results. Further, compared to FA analysis, NDI and ODI gave a pattern of results that was more regionally specific and were able to capture additional discriminative voxels that FA failed to identify. Finally, ODI from single-shell NODDI analysis, but not NDI, was found to reproduce the group differences from the multi-shell analysis. To conclude, by using a clinically feasible acquisition and analysis protocol, we demonstrated that NODDI is of added value to standard DTI, by revealing specific microstructural substrates to white matter changes detected with FA. As the (simpler) DTI model was more sensitive in identifying group differences, NODDI is recommended to be used complementary to DTI, thereby adding greater specificity regarding microstructural underpinnings of the differences. The finding that ODI abnormalities can be identified reliably using single-shell data may allow the retrospective analysis of standard DTI with NODDI.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sengupta2016,

title = {A Specialized Multi-Transmit Head Coil for High Resolution fMRI of the Human Visual Cortex at 7T.},

author = {Shubharthi Sengupta and Alard Roebroeck and Valentin G Kemper and Benedikt A Poser and Jan Zimmermann and Rainer Goebel and Gregor Adriany},

doi = {10.1371/journal.pone.0165418},

issn = {1932-6203 (Electronic)},

year  = {2016},

date = {2016-01-01},

journal = {PloS one},

volume = {11},

number = {12},

pages = {e0165418},

abstract = {PURPOSE: To design, construct and validate radiofrequency (RF) transmit and receive phased array coils for high-resolution visual cortex imaging at 7 Tesla. METHODS: A 4 channel transmit and 16 channel receive array was constructed on a conformal polycarbonate former. Transmit field efficiency and homogeneity were simulated and validated, along with the Specific Absorption Rate, using [Formula: see text] mapping techniques and electromagnetic simulations. Receiver signal-to-noise ratio (SNR), temporal SNR (tSNR) across EPI time series, g-factors for accelerated imaging and noise correlations were evaluated and compared with a commercial 32 channel whole head coil. The performance of the coil was further evaluated with human subjects through functional MRI (fMRI) studies at standard and submillimeter resolutions of upto 0.8mm isotropic. RESULTS: The transmit and receive sections were characterized using bench tests and showed good interelement decoupling, preamplifier decoupling and sample loading. SNR for the 16 channel coil was ∼ 1.5 times that of the commercial coil in the human occipital lobe, and showed better g-factor values for accelerated imaging. fMRI tests conducted showed better response to Blood Oxygen Level Dependent (BOLD) activation, at resolutions of 1.2mm and 0.8mm isotropic. CONCLUSION: The 4 channel phased array transmit coil provides homogeneous excitation across the visual cortex, which, in combination with the dual row 16 channel receive array, makes for a valuable research tool for high resolution anatomical and functional imaging of the visual cortex at 7T.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bastiani2016,

title = {Automatic Segmentation of Human Cortical Layer-Complexes and Architectural Areas Using Ex vivo Diffusion MRI and Its Validation.},

author = {Matteo Bastiani and Ana-Maria Oros-Peusquens and Arne Seehaus and Daniel Brenner and Klaus Möllenhoff and Avdo Celik and Jörg Felder and Hansjürgen Bratzke and Nadim J Shah and Ralf Galuske and Rainer Goebel and Alard Roebroeck},

doi = {10.3389/fnins.2016.00487},

issn = {1662-4548 (Print)},

year  = {2016},

date = {2016-01-01},

journal = {Frontiers in neuroscience},

volume = {10},

pages = {487},

abstract = {Recently, several magnetic resonance imaging contrast mechanisms have been shown to distinguish cortical substructure corresponding to selected cortical layers. Here, we investigate cortical layer and area differentiation by automatized unsupervised clustering of high-resolution diffusion MRI data. Several groups of adjacent layers could be distinguished in human primary motor and premotor cortex. We then used the signature of diffusion MRI signals along cortical depth as a criterion to detect area boundaries and find borders at which the signature changes abruptly. We validate our clustering results by histological analysis of the same tissue. These results confirm earlier studies which show that diffusion MRI can probe layer-specific intracortical fiber organization and, moreover, suggests that it contains enough information to automatically classify architecturally distinct cortical areas. We discuss the strengths and weaknesses of the automatic clustering approach and its appeal for MR-based cortical histology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Plantinga2016,

title = {Ultra-High Field MRI Post Mortem Structural Connectivity of the Human Subthalamic Nucleus, Substantia Nigra, and Globus Pallidus.},

author = {Birgit R Plantinga and Alard Roebroeck and Valentin G Kemper and Kâmil Uludağ and Maartje Melse and Jürgen Mai and Mark L Kuijf and Andreas Herrler and Ali Jahanshahi and Bart M Ter Haar Romeny and Yasin Temel},

doi = {10.3389/fnana.2016.00066},

issn = {1662-5129 (Print)},

year  = {2016},

date = {2016-01-01},

journal = {Frontiers in neuroanatomy},

volume = {10},

pages = {66},

abstract = {INTRODUCTION: The subthalamic nucleus, substantia nigra, and globus pallidus, three nuclei of the human basal ganglia, play an important role in motor, associative, and limbic processing. The network of the basal ganglia is generally characterized by a direct, indirect, and hyperdirect pathway. This study aims to investigate the mesoscopic nature of these connections between the subthalamic nucleus, substantia nigra, and globus pallidus and their surrounding structures. METHODS: A human post mortem brain specimen including the substantia nigra, subthalamic nucleus, and globus pallidus was scanned on a 7 T MRI scanner. High resolution diffusion weighted images were used to reconstruct the fibers intersecting the substantia nigra, subthalamic nucleus, and globus pallidus. The course and density of these tracks was analyzed. RESULTS: Most of the commonly established projections of the subthalamic nucleus, substantia nigra, and globus pallidus were successfully reconstructed. However, some of the reconstructed fiber tracks such as the connections of the substantia nigra pars compacta to the other included nuclei and the connections with the anterior commissure have not been shown previously. In addition, the quantitative tractography approach showed a typical degree of connectivity previously not documented. An example is the relatively larger projections of the subthalamic nucleus to the substantia nigra pars reticulata when compared to the projections to the globus pallidus internus. DISCUSSION: This study shows that ultra-high field post mortem tractography allows for detailed 3D reconstruction of the projections of deep brain structures in humans. Although the results should be interpreted carefully, the newly identified connections contribute to our understanding of the basal ganglia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Havlicek2015,

title = {Physiologically informed dynamic causal modeling of fMRI data.},

author = {Martin Havlicek and Alard Roebroeck and Karl Friston and Anna Gardumi and Dimo Ivanov and Kamil Uludag},

doi = {10.1016/j.neuroimage.2015.07.078},

issn = {1095-9572 (Electronic)},

year  = {2015},

date = {2015-11-01},

journal = {NeuroImage},

volume = {122},

pages = {355--372},

abstract = {The functional MRI (fMRI) signal is an indirect measure of neuronal activity. In order to deconvolve the neuronal activity from the experimental fMRI data, biophysical generative models have been proposed describing the link between neuronal activity and the cerebral blood flow (the neurovascular coupling), and further the hemodynamic response and the BOLD signal equation. These generative models have been employed both for single brain area deconvolution and to infer effective connectivity in networks of multiple brain areas. In the current paper, we introduce a new fMRI model inspired by experimental observations about the physiological underpinnings of the BOLD signal and compare it with the generative models currently used in dynamic causal modeling (DCM), a widely used framework to study effective connectivity in the brain. We consider three fundamental aspects of such generative models for fMRI: (i) an adaptive two-state neuronal model that accounts for a wide repertoire of neuronal responses during and after stimulation; (ii) feedforward neurovascular coupling that links neuronal activity to blood flow; and (iii) a balloon model that can account for vascular uncoupling between the blood flow and the blood volume. Finally, we adjust the parameterization of the BOLD signal equation for different magnetic field strengths. This paper focuses on the form, motivation and phenomenology of DCMs for fMRI and the characteristics of the various models are demonstrated using simulations. These simulations emphasize a more accurate modeling of the transient BOLD responses - such as adaptive decreases to sustained inputs during stimulation and the post-stimulus undershoot. In addition, we demonstrate using experimental data that it is necessary to take into account both neuronal and vascular transients to accurately model the signal dynamics of fMRI data. By refining the models of the transient responses, we provide a more informed perspective on the underlying neuronal process and offer new ways of inferring changes in local neuronal activity and effective connectivity from fMRI.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bittner2015,

title = {The When and Where of Working Memory Dysfunction in Early-Onset Schizophrenia-A Functional Magnetic Resonance Imaging Study.},

author = {Robert A Bittner and David E J Linden and Alard Roebroeck and Fabian Härtling and Anna Rotarska-Jagiela and Konrad Maurer and Rainer Goebel and Wolf Singer and Corinna Haenschel},

doi = {10.1093/cercor/bhu050},

issn = {1460-2199 (Electronic)},

year  = {2015},

date = {2015-09-01},

journal = {Cerebral cortex (New York, N.Y. : 1991)},

volume = {25},

number = {9},

pages = {2494--2506},

abstract = {Behavioral evidence indicates that working memory (WM) in schizophrenia is already impaired at the encoding stage. However, the neurophysiological basis of this primary deficit remains poorly understood. Using event-related fMRI, we assessed differences in brain activation and functional connectivity during the encoding, maintenance and retrieval stages of a visual WM task with 3 levels of memory load in 17 adolescents with early-onset schizophrenia (EOS) and 17 matched controls. The amount of information patients could store in WM was reduced at all memory load levels. During encoding, activation in left ventrolateral prefrontal cortex (VLPFC) and extrastriate visual cortex, which in controls positively correlated with the amount of stored information, was reduced in patients. Additionally, patients showed disturbed functional connectivity between prefrontal and visual areas. During retrieval, right inferior VLPFC hyperactivation was correlated with hypoactivation of left VLPFC in patients during encoding. Visual WM encoding is disturbed by a failure to adequately engage a visual-prefrontal network critical for the transfer of perceptual information into WM. Prefrontal hyperactivation appears to be a secondary consequence of this primary deficit. Isolating the component processes of WM can lead to more specific neurophysiological markers for translational efforts seeking to improve the treatment of cognitive dysfunction in schizophrenia.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Frankort2015,

title = {Neural predictors of chocolate intake following chocolate exposure.},

author = {Astrid Frankort and Anne Roefs and Nicolette Siep and Alard Roebroeck and Remco Havermans and Anita Jansen},

doi = {10.1016/j.appet.2014.12.204},

issn = {1095-8304 (Electronic)},

year  = {2015},

date = {2015-04-01},

journal = {Appetite},

volume = {87},

pages = {98--107},

abstract = {Previous studies have shown that one's brain response to high-calorie food cues can predict long-term weight gain or weight loss. The neural correlates that predict food intake in the short term have, however, hardly been investigated. This study examined which brain regions' activation predicts chocolate intake after participants had been either exposed to real chocolate or to control stimuli during approximately one hour, with interruptions for fMRI measurements. Further we investigated whether the variance in chocolate intake could be better explained by activated brain regions than by self-reported craving. In total, five brain regions correlated with subsequent chocolate intake. The activation of two reward regions (the right caudate and the left frontopolar cortex) correlated positively with intake in the exposure group. The activation of two regions associated with cognitive control (the left dorsolateral and left mid-dorsolateral PFC) correlated negatively with intake in the control group. When the regression analysis was conducted with the exposure and the control group together, an additional region's activation (the right anterior PFC) correlated positively with chocolate intake. In all analyses, the intake variance explained by neural correlates was above and beyond the variance explained by self-reported craving. These results are in line with neuroimaging research showing that brain responses are a better predictor of subsequent intake than self-reported craving. Therefore, our findings might provide for a missing link by associating brain activation, previously shown to predict weight change, with short-term intake.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Timmers2015,

title = {White matter microstructure pathology in classic galactosemia revealed by neurite orientation dispersion and density imaging.},

author = {Inge Timmers and Hui Zhang and Matteo Bastiani and Bernadette M Jansma and Alard Roebroeck and M Estela Rubio-Gozalbo},

doi = {10.1007/s10545-014-9780-x},

issn = {1573-2665 (Electronic)},

year  = {2015},

date = {2015-03-01},

journal = {Journal of inherited metabolic disease},

volume = {38},

number = {2},

pages = {295--304},

abstract = {White matter abnormalities have been observed in patients with classic galactosemia, an inborn error of galactose metabolism. However, magnetic resonance imaging (MRI) data collected in the past were generally qualitative in nature. Our objective was to investigate white matter microstructure pathology and examine correlations with outcome and behaviour in this disease, by using multi-shell diffusion weighted imaging. In addition to standard diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI) was used to estimate density and orientation dispersion of neurites in a group of eight patients (aged 16-21 years) and eight healthy controls (aged 15-20 years). Extensive white matter abnormalities were found: neurite density index (NDI) was lower in the patient group in bilateral anterior areas, and orientation dispersion index (ODI) was increased mainly in the left hemisphere. These specific regional profiles are in agreement with the cognitive profile observed in galactosemia, showing higher order cognitive impairments, and language and motor impairments, respectively. Less favourable white matter properties correlated positively with age and age at onset of diet, and negatively with behavioural outcome (e.g. visual working memory). To conclude, this study provides evidence of white matter pathology regarding density and dispersion of neurites in these patients. The results are discussed in light of suggested pathophysiological mechanisms.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Seehaus2015,

title = {Histological validation of high-resolution DTI in human post mortem tissue.},

author = {Arne Seehaus and Alard Roebroeck and Matteo Bastiani and Lúcia Fonseca and Hansjürgen Bratzke and Nicolás Lori and Anna Vilanova and Rainer Goebel and Ralf Galuske},

doi = {10.3389/fnana.2015.00098},

issn = {1662-5129 (Print)},

year  = {2015},

date = {2015-01-01},

journal = {Frontiers in neuroanatomy},

volume = {9},

pages = {98},

abstract = {Diffusion tensor imaging (DTI) is amongst the simplest mathematical models available for diffusion magnetic resonance imaging, yet still by far the most used one. Despite the success of DTI as an imaging tool for white matter fibers, its anatomical underpinnings on a microstructural basis remain unclear. In this study, we used 65 myelin-stained sections of human premotor cortex to validate modeled fiber orientations and oft used microstructure-sensitive scalar measures of DTI on the level of individual voxels. We performed this validation on high spatial resolution diffusion MRI acquisitions investigating both white and gray matter. We found a very good agreement between DTI and myelin orientations with the majority of voxels showing angular differences less than 10°. The agreement was strongest in white matter, particularly in unidirectional fiber pathways. In gray matter, the agreement was good in the deeper layers highlighting radial fiber directions even at lower fractional anisotropy (FA) compared to white matter. This result has potentially important implications for tractography algorithms applied to high resolution diffusion MRI data if the aim is to move across the gray/white matter boundary. We found strong relationships between myelin microstructure and DTI-based microstructure-sensitive measures. High FA values were linked to high myelin density and a sharply tuned histological orientation profile. Conversely, high values of mean diffusivity (MD) were linked to bimodal or diffuse orientation distributions and low myelin density. At high spatial resolution, DTI-based measures can be highly sensitive to white and gray matter microstructure despite being relatively unspecific to concrete microarchitectural aspects.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bastiani2015,

title = {Unraveling the multiscale structural organization and connectivity of the human brain: the role of diffusion MRI.},

author = {Matteo Bastiani and Alard Roebroeck},

doi = {10.3389/fnana.2015.00077},

issn = {1662-5129 (Print)},

year  = {2015},

date = {2015-01-01},

journal = {Frontiers in neuroanatomy},

volume = {9},

pages = {77},

abstract = {The structural architecture and the anatomical connectivity of the human brain show different organizational principles at distinct spatial scales. Histological staining and light microscopy techniques have been widely used in classical neuroanatomical studies to unravel brain organization. Using such techniques is a laborious task performed on 2-dimensional histological sections by skilled anatomists possibly aided by semi-automated algorithms. With the recent advent of modern magnetic resonance imaging (MRI) contrast mechanisms, cortical layers and columns can now be reliably identified and their structural properties quantified post-mortem. These developments are allowing the investigation of neuroanatomical features of the brain at a spatial resolution that could be interfaced with that of histology. Diffusion MRI and tractography techniques, in particular, have been used to probe the architecture of both white and gray matter in three dimensions. Combined with mathematical network analysis, these techniques are increasingly influential in the investigation of the macro-, meso-, and microscopic organization of brain connectivity and anatomy, both in vivo and ex vivo. Diffusion MRI-based techniques in combination with histology approaches can therefore support the endeavor of creating multimodal atlases that take into account the different spatial scales or levels on which the brain is organized. The aim of this review is to illustrate and discuss the structural architecture and the anatomical connectivity of the human brain at different spatial scales and how recently developed diffusion MRI techniques can help investigate these.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}