The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease ...(PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.
•The thalamic target for surgery for tremor is not readily visible on conventional MRI.•Probabilistic tractography is used to segment the thalamus based on connectivity.•The best target area is connected to the contralateral dentate cerebellar nucleus.•GPU processing is used to segment the thalamus in a clinically feasible timescale.•This technique can map out the DRT tract with clear mesencephalic crossing.
Arterial spin labeling (ASL) has undergone significant development since its inception, with a focus on improving standardization and reproducibility of its acquisition and quantification. In a ...community-wide effort towards robust and reproducible clinical ASL image processing, we developed the software package ExploreASL, allowing standardized analyses across centers and scanners.
The procedures used in ExploreASL capitalize on published image processing advancements and address the challenges of multi-center datasets with scanner-specific processing and artifact reduction to limit patient exclusion. ExploreASL is self-contained, written in MATLAB and based on Statistical Parameter Mapping (SPM) and runs on multiple operating systems. To facilitate collaboration and data-exchange, the toolbox follows several standards and recommendations for data structure, provenance, and best analysis practice.
ExploreASL was iteratively refined and tested in the analysis of >10,000 ASL scans using different pulse-sequences in a variety of clinical populations, resulting in four processing modules: Import, Structural, ASL, and Population that perform tasks, respectively, for data curation, structural and ASL image processing and quality control, and finally preparing the results for statistical analyses on both single-subject and group level. We illustrate ExploreASL processing results from three cohorts: perinatally HIV-infected children, healthy adults, and elderly at risk for neurodegenerative disease. We show the reproducibility for each cohort when processed at different centers with different operating systems and MATLAB versions, and its effects on the quantification of gray matter cerebral blood flow.
ExploreASL facilitates the standardization of image processing and quality control, allowing the pooling of cohorts which may increase statistical power and discover between-group perfusion differences. Ultimately, this workflow may advance ASL for wider adoption in clinical studies, trials, and practice.
The assessment of language lateralization has become widely used when planning neurosurgery close to language areas, due to individual specificities and potential influence of brain pathology. ...Functional magnetic resonance imaging (fMRI) allows non-invasive and quantitative assessment of language lateralization for presurgical planning using a laterality index (LI). However, the conventional method is limited by the dependence of the LI on the chosen activation threshold. To overcome this limitation, different threshold-independent LI calculations have been reported. The purpose of this study was to propose a simplified approach to threshold-independent LI calculation and compare it with three previously reported methods on the same cohort of subjects. Fifteen healthy subjects, who performed picture naming, verb generation, and word fluency tasks, were scanned. LI values were calculated for all subjects using four methods, and considering either the whole hemisphere or an atlas-defined language area. For each method, the subjects were ranked according to the calculated LI values, and the obtained rankings were compared. All LI calculation methods agreed in differentiating strong from weak lateralization on both hemispheric and regional scales (Spearman's correlation coefficients 0.59-1.00). In general, a more lateralized activation was found in the language area than in the whole hemisphere. The new method is well suited for application in the clinical practice as it is simple to implement, fast, and robust. The good agreement between LI calculation methods suggests that the choice of method is not key. Nevertheless, it should be consistent to allow a relative comparison of language lateralization between subjects.
To validate proposed magnetic resonance (MR) imaging features of Crohn disease activity against a histopathologic reference.
Ethical permission was given by the University College London hospital ...ethics committee, and informed written consent was obtained from all participants. Preoperative MR imaging was performed in 18 consecutive patients with Crohn disease undergoing elective small-bowel resection. The Harvey-Bradshaw index, the C-reactive protein level, and disease chronicity were recorded. The resected bowel was retrospectively identified at preoperative MR imaging, and wall thickness, mural and lymph node/cerebrospinal fluid (CSF) signal intensity ratios on T2-weighted fat-saturated images, gadolinium-based contrast material uptake, enhancement pattern, and mesenteric signal intensity on T2-weighted fat-saturated images were recorded. Precise histologic matching was achieved by imaging the ex vivo surgical specimens. Histopathologic grading of acute inflammation with the acute inflammatory score (AIS) (on the basis of mucosal ulceration, edema, and quantity and depth of neutrophilic infiltration) and the degree of fibrostenosis was performed at each site, and results were compared with MR imaging features. Data were analyzed by using linear regression with robust standard errors of the estimate.
AIS was positively correlated with mural thickness and mural/CSF signal intensity ratio on T2-weighted fat-saturated images (P < .001 and P = .003, respectively) but not with mural enhancement at 30 and 70 seconds (P = .50 and P = .73, respectively). AIS was higher with layered mural enhancement (P < .001), a pattern also commonly associated with coexisting fibrostenosis (75%). Mural/CSF signal intensity ratio on T2-weighted fat-saturated images was higher in histologically edematous bowel than in nonedematous bowel (P = .04). There was no correlation between any lymph node characteristic and AIS.
Increasing mural thickness, high mural signal intensity on T2-weighted fat-saturated images, and a layered pattern of enhancement reflect histologic features of acute small-bowel inflammation in Crohn disease.
J-difference-edited spectroscopy is a valuable approach for the detection of low-concentration metabolites with magnetic resonance spectroscopy (MRS). Currently, few edited MRS studies are performed ...in neonates due to suboptimal signal-to-noise ratio, relatively long acquisition times, and vulnerability to motion artifacts. Nonetheless, the technique presents an exciting opportunity in pediatric imaging research to study rapid maturational changes of neurotransmitter systems and other metabolic systems in early postnatal life. Studying these metabolic processes is vital to understanding the widespread and rapid structural and functional changes that occur in the first years of life. The overarching goal of this review is to provide an introduction to edited MRS for neonates, including the current state-of-the-art in editing methods and editable metabolites, as well as to review the current literature applying edited MRS to the neonatal brain. Existing challenges and future opportunities, including the lack of age-specific reference data, are also discussed.
•First simultaneous measurement of GABA+, Glx and GSH in the neonatal human brain.•Robust metabolic estimation in neonates requires a specific quantification strategy.•GABA+ has a doublet peak in ...neonates indicating lower macromolecular contributions.•Future application can inform about pathophysiology in neurodevelopment.
Balance between inhibitory and excitatory neurotransmitter systems and the protective role of the major antioxidant glutathione (GSH) are central to early healthy brain development. Disruption has been implicated in the early life pathophysiology of psychiatric disorders and neurodevelopmental conditions including Autism Spectrum Disorder.
Edited magnetic resonance spectroscopy (MRS) methods such as HERMES have great potential for providing important new non-invasive insights into these crucial processes in human infancy. In this work, we describe a systematic approach to minimise the impact of specific technical challenges inherent to acquiring MRS data in a neonatal population, including automatic segmentation, full tissue-correction and optimised GABA+ fitting and consider the minimum requirements for a robust edited-MRS acquisition. With this approach we report for the first time simultaneous GABA+, Glx (glutamate + glutamine) and GSH concentrations in the neonatal brain (n = 18) in two distinct regions (thalamus and anterior cingulate cortex (ACC)) using edited MRS at 3T.
The improved sensitivity provided by our method allows specific regional neurochemical differences to be identified including: significantly lower Glx and GSH ratios to total creatine in the thalamus compared to the ACC (p < 0.001 for both), and significantly higher GABA+ and Glx levels in the ACC following tissue-correction (p < 0.01). Furthermore, in contrast to adult GABA+ which can typically be accurately fitted with a single peak, all neonate spectra displayed a characteristic doublet GABA+ peak at 3 ppm, indicating a lower macromolecule (MM) contribution to the 3 ppm signal in neonates. Relatively high group-level variance shows the need to maximise voxel size/acquisition time in edited neonatal MRS acquisitions for robust estimation of metabolites.
Application of this method to study how these levels and balance are altered by early-life brain injury or genetic risk can provide important new knowledge about the pathophysiology underlying neurodevelopmental disorders.
•Novel methodology and software for MR-PET registration uncertainty analysis.•Registration software had the biggest effect on MR-PET registration precision, followed by reconstruction parameters ...(i.e., iterations, smoothing) and PET count level.•PVC can significantly improve the PET signal, but since it relies on precise MR-PET registration, it also increases PET signal variability and hence care should be taken when using it.
Accurate regional brain quantitative PET measurements, particularly when using partial volume correction, rely on robust image registration between PET and MR images. We argue here that the precision, and hence the uncertainty, of MR-PET image registration is mainly driven by the registration implementation and the quality of PET images due to their lower resolution and higher noise compared to the structural MR images. We propose a dedicated uncertainty analysis for quantifying the precision of MR-PET registration, centred around the bootstrap resampling of PET list-mode events to generate multiple PET image realisations with different noise (count) levels. The effects of PET image reconstruction parameters, such as the use of attenuation and scatter corrections and different number of iterations, on the precision and accuracy of MR-PET registration were investigated. In addition, the performance of four software packages with their default settings for rigid inter-modality image registration were considered: NiftyReg, Vinci, FSL and SPM. Four distinct PET image distributions made of two early time frames (similar to cortical FDG) and two late frames using two amyloid PET dynamic acquisitions of one amyloid positive and one amyloid negative participants were investigated.
For the investigated four PET frames, the biggest impact on the uncertainty was observed between registration software packages (up to 10-fold difference in precision) followed by the reconstruction parameters. On average, the lowest uncertainty for different PET frames and brain regions was observed with SPM and two iterations of fully quantitative image reconstruction. The observed uncertainty for the varying PET count-level (from 5% to 60%) was slightly lower than for the reconstruction parameters. We also observed that the registration uncertainty in quantitative PET analysis depends on amyloid status of the considered PET frames, with increased uncertainty (up to three times) when using post-reconstruction partial volume correction. This analysis is applicable for PET data obtained from either PET/MR or PET/CT scanners.
The neurodevelopmental phenotype in Down Syndrome (DS), or Trisomy 21, is variable including a wide spectrum of cognitive impairment and a high risk of early-onset Alzheimer's disease (AD). A key ...metabolite of interest within the brain in DS is Myo-inositol (mIns). The NA+/mIns co-transporter is located on human chromosome 21 and is overexpressed in DS. In adults with DS, elevated brain mIns was previously associated with cognitive impairment and proposed as a risk marker for progression to AD. However, it is unknown if brain mIns is increased earlier in development.
The aim of this study was to estimate mIns concentration levels and key brain metabolites N-acetylaspartate (NAA), Choline (Cho) and Creatine (Cr) in the developing brain in DS and aged-matched controls. We used in vivo magnetic resonance spectroscopy (MRS) in neonates with DS (n = 12) and age-matched controls (n = 26) scanned just after birth (36–45 weeks postmenstrual age). Moreover, we used Mass Spectrometry in early (10–20 weeks post conception) ex vivo fetal brain tissue samples from DS (n = 14) and control (n = 30) cases.
Relative to Cho and Cr, we report elevated ratios of mIns in vivo in the basal ganglia/thalamus, in neonates with DS, when compared to age-matched typically developing controls. Glycine concentration ratios Gly/Cr and Cho/Cr also appear elevated. We observed elevated mIns in the ex vivo fetal cortical brain tissue in DS compared with controls.
In conclusion, a higher level of brain mIns was evident as early as 10 weeks post conception and was measurable in vivo from 36 weeks post-menstrual age. Future work will determine if this early difference in metabolites is linked to cognitive outcomes in childhood or has utility as a potential treatment biomarker for early intervention.
•Myo-inositol is elevated in fetal cortical DS brain.•Elevated myo-inositol was detected in the neonatal DS brain using MR spectroscopy.•Elevated Choline/Creatine and Glycine/Creatine was also present in DS neonatal brain.
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