Montreal Neurological Institute Space Research Articles

Automatically targeting the dorsolateral subthalamic nucleus for functional connectivity-guided rTMS therapy

Aim: Many resting-state functional magnetic resonance imaging (rs-fMRI) studies have provided evidence that repetitive transcranial magnetic stimulation (rTMS) exerts treatment effects via functional connectivity (FC) from a superficial stimulation target to a deep effective region. The dorsolateral subthalamic nucleus (DL-STN) is an effective target in deep brain stimulation surgery for Parkinson’s disease (PD), but its targeting highly depends on well-trained neurosurgeons and is not easily used for FC-guided rTMS. We aimed to devise a method for automatically localizing the DL-STN, and further develop a one-stop plug-in of rs-fMRI FC analysis to assist future individualized FC-guided rTMS. Methods: Based on structural and iron-sensitive MRI of 78 participants, two raters defined the DL-STN coordinates with very high reliability. The averaged coordinates in the standard Montreal Neurological Institute (MNI) space were: left DL-STN, x: -11.89 ± 0.82, y: -14.51 ± 1.00, and z: -6.40 ± 1.01 and the right DL-STN, x: 12.53 ± 0.77, y: -13.97 ± 0.86, and z: -6.57 ± 0.99. As the individual distances from the averaged coordinates were less than 3 mm (within one voxel for most rs-fMRI studies) for all 78 participants, we defined the average coordinates as AutoSTN. We then developed a one-stop plug-in named Connectivity and Coordinates Converting Assistant Toolbox (CC-CAT) and performed AutoSTN FC analysis. Results: The AutoSTN seed showed significant FC with the motor cortices in all participants. Conclusion: The AutoSTN-based rs-fMRI FC could guide future rTMS on PD. The one-stop plug-in CC-CAT can be used for any FC-guided rTMS treatment.

Lesion Frequency Distribution Maps of Traumatic Axonal Injury on Early Magnetic Resonance Imaging after Moderate and Severe Traumatic Brain Injury and Associations to 12 Months Outcome.

Traumatic axonal injury (TAI) is a common finding on MRI in patients with moderate - severe traumatic brain injury (TBI), and the burden of TAI is associated with outcome in this patient group. Lesion mapping offers a way to combine imaging findings from numerous individual patients into common lesion maps where the findings from a whole patient cohort can be assessed. The aim of this study was to evaluate the spatial distribution of traumatic axonal injury (TAI) lesions on different MRI sequences and its associations to outcome with use of lesion mapping. 269 patients (8-70 years) with moderate or severe TBI traumatic brain injury and magnetic resonance imaging (MRI) within six weeks after injury were prospectively included. TAI lesions were evaluated and manually segmented on fluid-attenuated inversed recovery (FLAIR), diffusion weighted imaging (DWI) and either T2* gradient echo (T2*GRE) or susceptibility weighted imaging (SWI). The segmentations were registered to the Montreal Neurological Institute space and combined to lesion frequency distribution maps. Outcome was assessed with Glasgow Outcome Scale Extended (GOSE) score at 12 months. The frequency and distribution of TAI was assessed qualitatively by evaluated visually reading. Univariable associations to outcome was assessed qualitatively by visual reading evaluated visually and also quantitatively with use of voxel-based lesion-symptom mapping (VLSM). The highest frequency of TAI was found in the posterior half of corpus callosum. The frequency of TAI was higher in the frontal- and temporal lobes than in the parietal- and occipital lobes, and in the upper parts of the brainstem than in the lower. On At the group level, all the voxels in mesencephalon had TAI on FLAIR. The patients with poorest outcome (GOSE scores ≤ 4) had higher frequencies of TAI. On VLSM, poor outcome was associated with TAI lesions univariable associations to outcome was found bilaterally in the splenium, and in the right side of tectum, tegmental mesencephalon and pons. With this study, we present lesion frequency distribution maps of TAI in a large cohort of patients with moderate and severe TBI. In conclusion, we found the highest higher frequency of TAI in posterior corpus callosum, and TAI in splenium, mesencephalon and pons were associated to with poor outcome. In the future, integration into picture archiving systems would enable comparison of individual patient maps with If lesion frequency distribution maps containing outcome information based on imaging findings from numerous patients in the future can be compared to the imaging findings from individual patients, it would offer a new tool in the clinical work-up and outcome prediction of TBI patient. Key Words: Brain injuries, traumatic; Diffuse axonal injury; Neuroimaging; Brain mapping; Artificial intelligence.

Magnetoencephalography Atlas Viewer for Dipole Localization and Viewing.

Magnetoencephalography (MEG) is a noninvasive neuroimaging technique widely recognized for epilepsy and tumor mapping. MEG clinical reporting requires a multidisciplinary team, including expert input regarding each dipole's anatomic localization. Here, we introduce a novel tool, the "Magnetoencephalography Atlas Viewer" (MAV), which streamlines this anatomical analysis. The MAV normalizes the patient's Magnetic Resonance Imaging (MRI) to the Montreal Neurological Institute (MNI) space, reverse-normalizes MNI atlases to the native MRI, identifies MEG dipole files, and matches dipoles' coordinates to their spatial location in atlas files. It offers a user-friendly and interactive graphical user interface (GUI) for displaying individual dipoles, groups, coordinates, anatomical labels, and a tri-planar MRI view of the patient with dipole overlays. It evaluated over 273 dipoles obtained in clinical epilepsy subjects. Consensus-based ground truth was established by three neuroradiologists, with a minimum agreement threshold of two. The concordance between the ground truth and MAV labeling ranged from 79% to 84%, depending on the normalization method. Higher concordance rates were observed in subjects with minimal or no structural abnormalities on the MRI, ranging from 80% to 90%. The MAV provides a straightforward MEG dipole anatomic localization method, allowing a nonspecialist to prepopulate a report, thereby facilitating and reducing the time of clinical reporting.

Specific-CT brain template construction and retrospective dosimetric comparison study in brain for nasopharyngeal carcinoma patients treated with IMRT or VMAT.

The current Radiotherapy (RT) technology still inevitably irradiated normal brain tissue, causing implicit radiation-induced injury. This study investigates the precise localization and the corresponding radiation dosage of brain regions susceptible to damage in nasopharyngeal carcinoma (NPC) patients following RT. Utilizing the Advanced Normalization Tools (ANTs) package, a computed tomography (CT) brain template was created in the standard Montreal Neurological Institute (MNI) space, based on 803 Chinese NPC patients (T0~T4) who underwent RT. With this template, all patients' CT and RTdose data were registered to the MNI space, and the RTdose distribution characteristics in normal brain tissues were compared for NPC patients treated with Intensity-modulated radiotherapy (IMRT) or Volumetric Modulated Arc Therapy (VMAT), with patients' age and gender as covariates. Analysis of the average dosages indicated that certain areas within the Limbic, Temporal, and Posterior Lobes, the Brainstem, and the Cerebellum Posterior Lobe were exposed to doses exceeding 50 Gy. Inter-group analysis revealed that IMRT delivered higher doses than VMAT to brain regions anterior to the nasopharyngeal tumor, whereas VMAT affected the posterior regions more. Interestingly, VMAT showed a drawback in preserving the normal brain tissues for T4-stage patients. This revealed that the two treatment modalities have unique characteristics in preserving normal brain tissue, each with advantages. With better localization precision, the created CT brain template in MNI space may be beneficial for NPC patients' toxicity and dosimetric analyses.

Speech and lexico-semantic errors during direct cortical stimulation mapping of the language-dominant hemisphere: effects of object and action naming.

In this retrospective study, the authors aimed to establish the stereotactically defined probability distribution for speech (i.e., anarthria, speech arrest) and lexico-semantic errors (i.e., anomia) through direct cortical stimulation (DCS) by using two tasks: action naming and object naming. They also analyzed the patterns of interindividual variability in the localization of the language sites involved, and investigated whether any patient or lesion location factors were associated with greater variability. Eighty-one Italian-speaking patients who underwent awake surgery between 2010 and 2021 for low- and high-grade gliomas in eloquent areas of the language-dominant hemisphere were entered in the analyses. The intraoperative DCS protocol included automatic speech tasks, object naming, and action naming. The position of the tags, as depicted on the intraoperative video or photograph, was transposed into Montreal Neurological Institute space. Subsequently, a 2D scatterplot and cluster analysis were performed. Associations between various clinical and radiological characteristics and the quantity of positive stimulated sites were determined by univariate analyses using binary logistic regression. Associated variables (p < 0.2) were included in stepwise multivariate logistic regression with backward elimination (p < 0.05). A total of 1380 cortical sites were stimulated, with a positive response in 511 cases (37%). Most anarthric errors were triggered when stimulating the left precentral gyrus, and most speech arrest errors were elicited when stimulating the left posterior inferior frontal gyrus. Anomias were found in the left inferior frontal gyrus and in the posterior part of the left temporal lobe for object naming. DCS to the left dorsal premotor cortex elicited anomic errors for action naming. Anomias were also elicited during DCS to the left posterior temporal lobe, with both object and action naming. The distribution of speech and lexico-semantic errors is in line with the current literature. The action-naming results are new and mostly involve the dorsal premotor cortex. These findings stress the importance of maximizing the use of different language tasks during surgery, because even when looking for the same type of errors, different tasks may be better suited to map specific brain regions. DCS with action and object naming identifies more positive sites than object naming alone.

Voxel‐level of abnormal β‐amyloid accumulation and spatiotemporal distribution patterns in Alzheimer’s Disease

AbstractBackgroundThe spatial patterns of β‐amyloid (Aβ) accumulation are critical for early diagnosis and clinical trials of Alzheimer’s Disease (AD). In this study, we explored a new voxel‐level Aβ index and investigated spatial patterns of voxels with abnormal Aβ deposition in different stages of AD.MethodWe identified 944 ADNI participants with Aβ 18F‐florbetapir positron emission tomography (PET) image. All Aβ PET images were co‐registered with their corresponding magnetic resonance imaging (MRI) scans, intensity‐normalized to the whole cerebellum, and spatial‐normalized to the Montreal Neurological Institute (MNI) space. We defined the threshold of each voxel as the mean+2SD of 18F‐florbetapir PET images of 51 participants who were Aβ PET negative (A‐), CSF p‐Tau181 negative (T‐), hippocampal atrophy negative (N‐), and cognitively unimpaired (CU) at both baseline and follow‐up. The positive voxel number (NoVoxel+) was counted based on the threshold of each voxel. The cross‐sectional and longitudinal correlations between NoVoxel+ and cortical summary Aβ standard uptake value ratio (SUVR) were determined in A‐ and Aβ‐positive (A+) separately. We compared baseline NoVoxel+ among different stages of AD, as well as how it related to longitudinal changes of Aβ SUVR, CSF p‐Tau181, residual hippocampal volume (rHCV), temporal meta‐ROI cortical thickness, and preclinical Alzheimer cognitive composite (PACC) score, and follow‐up tau PET levels, controlling for age, sex and APOE4. Finally, we investigated the spatial patterns of NoVoxel+ in different stages of AD.ResultThe new Aβ index NoVoxel+ was strongly correlated with the cortical summary Aβ SUVR cross‐sectionally and longitudinally regardless of Aβ positivity (Figure 1). Cognitively impaired (MCI and dementia) individuals showed larger (p&lt;0.001) NoVoxel+ than the CU individuals, A+ group had greater NoVoxel+ than the A‐ group (Figure 2). NoVoxel+ was related to faster rates of increases in Aβ SUVR and CSF p‐Tau, decreases in rHCV, temporal meta‐ROI cortical thickness, and PACC. Abnormal Aβ voxels were primarily located in precuneus, medial orbital frontal and anterior/posterior cingulate regions in A‐/CU group (Figure 3).ConclusionThe proposed voxel‐level Aβ deposition NoVoxel+ may be useful to investigate the spatial and temporal patterns of Aβ accumulation in AD, particularly in early amyloidosis stage.

Deep brain stimulation for Tourette syndrome: modulation of the limbic-motor interface network.

Deep brain stimulation (DBS) is an effective treatment for medically refractory Tourette syndrome (TS). Several effective targets have been reported, but there is still controversy about the networks involved in the efficacy of DBS for TS. Here, the authors aimed to identify the basal ganglia-thalamo-cortical networks associated with tic and obsessive-compulsive behavior (OCB) improvement and the network link between the two main targets for TS. A retrospective analysis of 21 patients treated with pallidal and thalamic DBS was performed. Tics and OCB scores were recorded before and after DBS. The authors localized the electrodes in standard MNI (Montreal Neurological Institute) space and calculated the volume of tissue activated with the settings at the last follow-up to obtain areas of maximal improvement ("sweet spots") among all patients for the pallidal and thalamic targets. Tractography was used to show the white matter pathways associated with maximal tic and OCB improvement. Ten patients treated with pallidal DBS and 11 patients treated with thalamic DBS were included. Responder rates were 80% in the pallidal and 64% in the thalamic target groups. Sweet spots for tics and OCB clustered in several areas across the basal ganglia and thalamus delineated two main networks. Tic reduction in the pallidal target mapped to a limbic pallidothalamic network and in the thalamic target to the premotor thalamocortical network. Putting these two networks together will form the main output of the so-called limbic-motor interface network. However, OCB reduction mapped a dorsomedial prefrontal cortex/dorsal anterior cingulate (dmPFC/dACC) network. The authors demonstrated the involvement of the limbic-motor interface network during effective DBS for tics in patients with TS. OCB redution was associated with the additional involvement of dmPFC/dACC connections passing dorsal to the head of the globus pallidus pars externa on its way to the thalamus and midbrain.

Adverse Life Experiences and Brain Function

Adverse life experiences have been proposed to contribute to diverse mental health problems through an association with corticolimbic functioning. Despite compelling evidence from animal models, findings from studies in humans have been mixed; activation likelihood estimation (ALE) meta-analyses have failed to identify a consistent association of adverse events with brain function. To investigate the association of adversity exposure with altered brain reactivity using multilevel kernel density analyses (MKDA), a meta-analytic approach considered more robust than ALE to small sample sizes and methodological differences between studies. Searches were conducted using PsycInfo, Medline, EMBASE, and Web of Science from inception through May 4, 2022. The following search term combinations were used for each database: trauma, posttraumatic stress disorder (PTSD), abuse, maltreatment, poverty, adversity, or stress; and functional magnetic resonance imaging (fMRI) or neuroimaging; and emotion, emotion regulation, memory, memory processing, inhibitory control, executive functioning, reward, or reward processing. Task-based fMRI studies within 4 domains (emotion processing, memory processing, inhibitory control, and reward processing) that included a measure of adverse life experiences and whole-brain coordinate results reported in Talairach or Montreal Neurological Institute space were included. Conference abstracts, books, reviews, meta-analyses, opinions, animal studies, articles not in English, and studies with fewer than 5 participants were excluded. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guideline, 2 independent reviewers assessed abstracts and full-text articles for entry criteria. A third reviewer resolved conflicts and errors in data extraction. Data were pooled using a random-effects model and data analysis occurred from August to November 2022. Peak activation x-axis (left-right), y-axis (posterior-anterior), and z-axis (inferior-superior) coordinates were extracted from all studies and submitted to MKDA meta-analyses. A total of 83 fMRI studies were included in the meta-analysis, yielding a combined sample of 5242 participants and 801 coordinates. Adversity exposure was associated with higher amygdala reactivity (familywise error rate corrected at P < .001; x-axis = 22; y-axis = -4; z-axis = -17) and lower prefrontal cortical reactivity (familywise error rate corrected at P < .001; x-axis = 10; y-axis = 60; z-axis = 10) across a range of task domains. These altered responses were only observed in studies that used adult participants and were clearest among those who had been exposed to severe threat and trauma. In this meta-analysis of fMRI studies of adversity exposure and brain function, prior adversity exposure was associated with altered adult brain reactivity to diverse challenges. These results might better identify how adversity diminishes the ability to cope with later stressors and produces enduring susceptibility to mental health problems.

MNI2CPC: A probabilistic cortex-to-scalp mapping for non-invasive brain stimulation targeting

BackgroundSynthesis of neural imaging information from many studies is valuable for identifying stable cortical targets for non-invasive brain stimulation (NIBS). Typically, these targets are specified in Montreal Neurological Institute (MNI) standard brain space. However, in practical NIBS applications, localizing MNI cortical targets often relies on the International 10–20 system or heuristic scalp approaches, which often lacks precision or applies only to specific targets. Objective/hypothesisWe aim to establish a probabilistic mapping from any cortical target in MNI space to continuous proportional coordinate (CPC) standard scalp space (MNI2CPC) and assess the performance of this mapping for NIBS targeting. MethodsThe MNI2CPC mapping was calculated based on a large MRI dataset (n = 114). Its targeting error was evaluated via cross-individual validation using a leave-one-out approach, as well as through independent validation across race (n = 27) and across patient (n = 58) cohorts. ResultsThe cross-individual validation demonstrated targeting errors of 4.03 ± 0.69 mm on the scalp and 3.30 ± 0.59 mm in the cortex. For independent cohorts, targeting errors were 4.71 ± 0.81 mm (scalp) and 3.85 ± 0.64 mm (cortex) across race, and 4.66 ± 0.77 mm (scalp) and 3.77 ± 0.61 mm (cortex) across patient. We publish a free online tool to enable querying of the CPC coordinate for any given MNI cortical target. The resulting CPC coordinates enable rapid and accurate manual localization on the scalp in a user-friendly manner. ConclusionsThe MNI2CPC mapping developed in this study allows for manual localization of any MNI cortical target, which improves the accessibility and ease of application of NIBS in diverse settings.

A right convergence area of the prefrontal lobe is involved in the improvement of semantic fluency in patients with post-stroke aphasia

ABSTRACT Objectives This study aimed to longitudinally observe the improvement mechanism of semantic fluency in subacute post-stroke aphasia (PSA) patients using resting-state functional magnetic resonance imaging (rs-fMRI). Methods Twelve PSA patients, about one month after onset, were enrolled in this study and received speech-language therapy (SLT) for one month. Auditory comprehension and semantic fluency were evaluated using the Western Aphasia Battery (WAB) and the Animal Fluency Test. Before and after treatment, rs-fMRI data were collected, and the dice similarity coefficient was used to measure the spatial similarity between each patient’s lesion and a reference lesion. The left posterior inferior temporal gyrus (pITG) was used as a seed to calculate the normalized functional connectivity in whole-brain voxel analysis using DPABI software for statistical analysis. Results The dice similarity coefficient between each patient’s lesion and the reference lesion showed moderate to high intensity (0.57 ± 0.14) in the Montreal Neurological Institute space. After treatment, we found a significant increase in functional connectivity between the left pITG and the right prefrontal lobe convergence area (peak t = 8.219, Gaussian random field multiple comparison correction, voxel p < 0.001, cluster p < 0.05). The increase in functional connectivity was negatively correlated with the improvement in auditory comprehension (r =–0.707, p = 0.033) and positively correlated with the improvement in semantic fluency (r = 0.79, p = 0.02). Conclusion The improvement of semantic fluency in subacute PSA patients may require the participation of the right convergence area of the prefrontal lobe.

A detailed dosimetric comparative study of IMRT and VMAT in normal brain tissues for nasopharyngeal carcinoma patients treated with radiotherapy.

Radiotherapy (RT) is the primary treatment for nasopharyngeal carcinoma (NPC). However, it can cause implicit RT-induced injury by irradiating normal brain tissue. To date, there have been no detailed reports on the radiated exact location in the brain, the corresponding radiation dose, and their relationship. We analyzed 803 Chinese NPC patients treated with RT and used a CT brain template in a Montreal Neurological Institute (MNI) space to compare the group differences in RT dose distribution for different RT technologies (IMRT or VMAT). Brain regions that received high doses (>50 Gy) of radiation were mainly located in parts of the temporal and limbic lobes, where radioactive damage often occurs. Brain regions that accepted higher doses with IMRT were mainly located near the anterior region of the nasopharyngeal tumor, while brain regions that accepted higher doses with VMAT were mainly located near the posterior region of the tumor. No significant difference was detected between IMRT and VMAT for T1 stage patients. For T2 stage patients, differences were widely distributed, with VMAT showing a significant dose advantage in protecting the normal brain tissue. For T3 stage patients, VMAT showed an advantage in the superior temporal gyrus and limbic lobe, while IMRT showed an advantage in the posterior cerebellum. For T4 stage patients, VMAT showed a disadvantage in protecting the normal brain tissue. These results indicate that IMRT and VMAT have their own advantages in sparing different organs at risk (OARs) in the brain for different T stages of NPC patients treated with RT. Our approach for analyzing dosimetric characteristics in a standard MNI space for Chinese NPC patients provides greater convenience in toxicity and dosimetry analysis with superior localization accuracy. Using this method, we found interesting differences from previous reports: VMAT showed a disadvantage in protecting the normal brain tissue for T4 stage NPC patients.

Direct localization and delineation of human pedunculopontine nucleus based on a self-supervised magnetic resonance image super-resolution method.

The pedunculopontine nucleus (PPN) is a small brainstem structure and has attracted attention as a potentially effective deep brain stimulation (DBS) target for the treatment of Parkinson's disease (PD). However, the in vivo location of PPN remains poorly described and barely visible on conventional structural magnetic resonance (MR) images due to a lack of high spatial resolution and tissue contrast. This study aims to delineate the PPN on a high-resolution (HR) atlas and investigate the visibility of the PPN in individual quantitative susceptibility mapping (QSM) images. We combine a recently constructed Montreal Neurological Institute (MNI) space unbiased QSM atlas (MuSus-100), with an implicit representation-based self-supervised image super-resolution (SR) technique to achieve an atlas with improved spatial resolution. Then guided by a myelin staining histology human brain atlas, we localize and delineate PPN on the atlas with improved resolution. Furthermore, we examine the feasibility of directly identifying the approximate PPN location on the 3.0-T individual QSM MR images. The proposed SR network produces atlas images with four times the higher spatial resolution (from 1 to 0.25 mm isotropic) without a training dataset. The SR process also reduces artifacts and keeps superb image contrast for further delineating small deep brain nuclei, such as PPN. Using the myelin staining histological atlas as guidance, we first identify and annotate the location of PPN on the T1-weighted (T1w)-QSM hybrid MR atlas with improved resolution in the MNI space. Then, we relocate and validate that the optimal targeting site for PPN-DBS is at the middle-to-caudal part of PPN on our atlas. Furthermore, we confirm that the PPN region can be identified in a set of individual QSM images of 10 patients with PD and 10 healthy young adults. The contrast ratios of the PPN to its adjacent structure, namely the medial lemniscus, on images of different modalities indicate that QSM substantially improves the visibility of the PPN both in the atlas and individual images. Our findings indicate that the proposed SR network is an efficient tool for small-size brain nucleus identification. HR QSM is promising for improving the visibility of the PPN. The PPN can be directly identified on the individual QSM images acquired at the 3.0-T MR scanners, facilitating a direct targeting of PPN for DBS surgery.

Longitudinal free-water changes in dementia with Lewy bodies (P8-11.007)

<h3>Objective:</h3> To characterize longitudinal diffusion microstructural changes in individuals with dementia with Lewy bodies (DLB). <h3>Background:</h3> Diffusion-weighted MRI (dMRI) examines tissue microstructure integrity and white matter pathways in vivo. Prior DLB studies focused on white matter or voxel-based techniques. Less is known about longitudinal white and grey matter microstructural changes in DLB. <h3>Design/Methods:</h3> dMRI scans were collected on individuals with DLB from the Mayo Clinic Longitudinal Imaging Biomarkers of DLB Program. Demographics, clinical evaluations and MRI were collected at baseline, and 12 or 24 months. Free-water (FW) and FW-corrected fractional anisotropy (FA_T) were analyzed in grey and white matter using 122 bilateral template regions and tracts of interest in Montreal Neurological Institute space. Primary outcomes were differences in FW and FA_T between baseline and 12 or 24 months. <h3>Results:</h3> We identified 23 individuals with DLB from baseline to 12 months [mean age 69.3 years (SD 9.5); 95.8% male], and 16 individuals from baseline to 24 months [mean age 67.5 years (SD 9.3); 100% male]. Participants at both time-points showed worsening in Montreal Cognitive Assessment and Movement Disorders Society Unified Parkinson’s Disease Rating Scale motor scores (<i>p</i>&lt;0.05). We found significant differences in FW, but not FA_T, from baseline to 12 months. Significant increases in FW at both time-points compared to baseline were observed in the insula, putamen, parahippocampal, and rolandic operculum regions (p&lt;0.05). We found more widespread microstructural changes from baseline to 24 months, with increased FW in the amygdala, entorhinal, mid and posterior cingulum, inferior frontal, hippocampal, pallidum, precuneus and retrosplenial regions (p&lt;0.05). We found decreased FA_T from baseline to 24 months in the cerebellar and superior occipital regions (<i>p</i>&lt;0.01). <h3>Conclusions:</h3> Longer follow-up at 24 months identified broader networks of free-water changes in individuals with DLB. More investigation is needed to evaluate the relationship of microstructural changes with clinical progression in DLB. <b>Disclosure:</b> Dr. Chiu has received research support from NIH/NIA. Mr. Chen has nothing to disclose. Dr. Wang has nothing to disclose. The institution of Dr. Armstrong has received research support from National Institute of Aging. The institution of Dr. Armstrong has received research support from Florida Department of Health. The institution of Dr. Armstrong has received research support from Lewy Body Dementia Association. Dr. Armstrong has received research support from Parkinson Foundation. Dr. Armstrong has received personal compensation in the range of $5,000-$9,999 for serving as a DSMB member with Alzheimer’s Clinical Trials Consortium. Dr. Armstrong has received personal compensation in the range of $5,000-$9,999 for serving as a DSMB member with Alzheimer’s Disease Cooperative Study. Dr. Armstrong has a non-compensated relationship as a Member, Scientific Advisory Council with Lewy Body Dementia Association that is relevant to AAN interests or activities. Dr. Boeve has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Rainwater Charitable Foundation. The institution of Dr. Boeve has received research support from Alector. The institution of Dr. Boeve has received research support from GE Healthcare. The institution of Dr. Boeve has received research support from Transposon. The institution of Dr. Boeve has received research support from Cognition Therapeutics. Dr. Boeve has received publishing royalties from a publication relating to health care. The institution of Dr. Kantarci has received research support from Eli Lilly. The institution of Dr. Kantarci has received research support from NIH. The institution of Dr. Kantarci has received research support from ADDF. David Vaillancourt has received personal compensation for serving as an employee of Automated Imaging Diagnostics. David Vaillancourt has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Wiley. The institution of David Vaillancourt has received research support from NIH. David Vaillancourt has received intellectual property interests from a discovery or technology relating to health care.

Intraoperative functional remapping unveils evolving patterns of cortical plasticity.

The efficiency with which the brain reorganizes following injury not only depends on the extent and the severity of the lesion, but also on its temporal features. It is established that diffuse low-grade gliomas (DLGG), brain tumours with a slow-growth rate, induce a compensatory modulation of the anatomo-functional architecture, making this kind of tumours an ideal lesion model to study the dynamics of neuroplasticity. Direct electrostimulation (DES) mapping is a well-tried procedure used during awake resection surgeries to identify and spare cortical epicentres which are critical for a range of functions. Because DLGG is a chronic disease, it inevitably relapses years after the initial surgery, and thus requires a second surgery to reduce tumour volume again. In this context, contrasting the cortical mappings obtained during two sequential neurosurgeries offers a unique opportunity to both identify and characterize the dynamic (i.e. re-evolving) patterns of cortical re-arrangements. Here, we capitalized on an unprecedented series of 101 DLGG patients who benefited from two DES-guided neurosurgeries usually spaced several years apart, resulting in a large DES dataset of 2082 cortical sites. All sites (either non-functional or associated with language, speech, motor, somatosensory and semantic processing) were recorded in Montreal Neurological Institute (MNI) space. Next, we used a multi-step approach to generate probabilistic neuroplasticity maps that reflected the dynamic rearrangements of cortical mappings from one surgery to another, both at the population and individual level. Voxel-wise neuroplasticity maps revealed regions with a relatively high potential of evolving reorganizations at the population level, including the supplementary motor area (SMA, Pmax = 0.63), the dorsolateral prefrontal cortex (dlPFC, Pmax = 0.61), the anterior ventral premotor cortex (vPMC, Pmax = 0.43) and the middle superior temporal gyrus (STG Pmax = 0.36). Parcel-wise neuroplasticity maps confirmed this potential for the dlPFC (Fisher's exact test, PFDR-corrected = 6.6 × 10-5), the anterior (PFDR-corrected = 0.0039) and the ventral precentral gyrus (PFDR-corrected = 0.0058). A series of clustering analyses revealed a topological migration of clusters, especially within the left dlPFC and STG (language sites); the left vPMC (speech arrest/dysarthria sites) and the right SMA (negative motor response sites). At the individual level, these dynamic changes were confirmed for the dlPFC (bilateral), the left vPMC and the anterior left STG (threshold free cluster enhancement, 5000 permutations, family-wise error-corrected). Taken as a whole, our results provide a critical insight into the dynamic potential of DLGG-induced continuing rearrangements of the cerebral cortex, with considerable implications for re-operations.

Stereotactical normalization with multiple templates representative of normal and Parkinson-typical reduction of striatal uptake improves the discriminative power of automatic semi-quantitative analysis in dopamine transporter SPECT

BackgroundThe specific binding ratio (SBR) of 123I-FP-CIT in the putamen is widely used to support the interpretation of dopamine transporter (DAT) SPECT. Automatic methods for computation of the putamen SBR often include stereotactical normalization of the individual DAT-SPECT image to an anatomical standard space. This study compared using a single 123I-FP-CIT template image as target for stereotactical normalization versus multiple templates representative of normal and different levels of Parkinson-typical reduction of striatal 123I-FP-CIT uptake.Methods1702 clinical 123I-FP-CIT SPECT images were stereotactically normalized (affine) to the anatomical space of the Montreal Neurological Institute (MNI) with SPM12 either using a single custom-made 123I-FP-CIT template representative of normal striatal uptake or using eight different templates representative of normal and different levels of Parkinson-typical reduction of striatal FP-CIT uptake with and without attenuation and scatter correction. In the latter case, SPM finds the linear combination of the multiple templates that best matches the patient’s image. The putamen SBR was obtained using hottest voxels analysis in large unilateral regions-of-interest predefined in MNI space. The histogram of the putamen SBR in the whole sample was fitted by the sum of two Gaussians. The power to differentiate between reduced and normal SBR was estimated by the effect size of the distance between the two Gaussians computed as the differences between their mean values scaled to their pooled standard deviation.ResultsThe effect size of the distance between the two Gaussians was 3.83 with the single template versus 3.96 with multiple templates for stereotactical normalization.ConclusionsMultiple templates representative of normal and different levels of Parkinson-typical reduction for stereotactical normalization of DAT-SPECT might provide improved separation between normal and reduced putamen SBR that could result in slightly improved power for the detection of nigrostriatal degeneration.

Altered cerebral neurovascular coupling in medication-overuse headache: A study combining multi-modal resting-state fMRI with 3D PCASL.

Structural and functional changes in the brain have been identified in individuals with medication-overuse headache (MOH) using MRI. However, it has not been clearly established whether neurovascular dysfunction occurs in MOH, which could be elucidated by examining neurovascular coupling (NVC) from the viewpoints of neuronal activity and cerebral blood flow. The aim of this study was to investigate potential alterations in NVC function of the brain in individuals with MOH using resting-state functional MRI (rs-fMRI) and 3D pseudo-continuous arterial spin labeling (3D PCASL) imaging techniques. A total of 40 patients with MOH and 32 normal controls (NCs) were recruited, and rs-fMRI and 3D PCASL data were obtained using a 3.0 T MR scanner. Standard preprocessing of the rs-fMRI data was performed to generate images representing regional homogeneity (ReHo), fractional amplitude of low-frequency fluctuation (fALFF), and degree centrality (DC); cerebral blood flow (CBF) images were generated using 3D PCASL sequence data. These functional maps were all normalized into Montreal Neurological Institute (MNI) space, and NVC was subsequently determined on the basis of Pearson correlation coefficients between the rs-fMRI maps (ReHo, fALFF, and DC) and CBF maps. The statistical significance of differences between the MOH and NC groups in terms of NVC in different brain regions was established via Z-test. Further analysis was performed to examine correlations between NVC in the brain regions with NVC dysfunction and clinical variables among patients with MOH. NVC mainly presented a negative correlation in patients with MOH and NCs. No significant difference between the two groups was detected in terms of average NVC over the entire gray matter area. However, several brain regions with significantly decreased NVC in patients with MOH compared to NCs were identified: the left orbital region of the superior frontal gyrus, the bilateral gyrus rectus, and the olfactory cortex (P < 0.05). A correlation analysis revealed that the DC of the brain regions with NVC dysfunction was significantly positively correlated with disease duration (r = 0.323, P = 0.042), and DC-CBF connectivity was negatively correlated with VAS score (r = -0.424, P = 0.035). The current study demonstrated that cerebral NVC dysfunction occurs in patients with MOH, and the NVC technique could function as a new imaging biomarker in headache research.

Evaluating the pharmacodynamic effects of padsevonil in healthy volunteers using simultaneous [11C]-UCB-J PET and MR Arterial Spin Labeling measurements

IntroductionIntegrated PET-MR scanners can measure simultaneously tracer binding, downstream cerebral blood flow (CBF) and neuronal activation. An integrated GE Signa PET-MR system was used to combine [11C]-UCB-J PET scanning with MR Arterial Spin Labeling (ASL) measurements to evaluate the effects of padsevonil (PSL) on SV2A occupancy and CBF simultaneously. MethodsPET-MR scanning was performed in 10 healthy controls (8M/2F; 27.6 ​± ​10.0 ​yrs) at baseline, and at two timepoints (post1: 2−24h and post2: 6−30h) after administration of a single PSL dose (6.2−100 ​mg). Dynamic [11C]-UCB-J PET scanning with arterial blood sampling was performed to estimate distribution volumes and corresponding SV2A occupancies. Simultaneously, MR ASL data were acquired and spatially normalized to Montreal Neurological Institute (MNI) space for voxel wise analysis while brain Volume-Of-Interest (VOI) were defined using a simplified Hammers atlas. ResultsPET measurements showed a SV2A occupancy range of 57–98% and 16−63% and a corresponding PSL plasma concentration range of 3.6–189.23 ​ng/mL and 1.3–9.8 ​ng/mL for post1 and post2, respectively. When comparing post1 to baseline ASL measurements, a VOI-based analysis detected a significant CBF decrease in thalamus, insula, cerebellum, posterior cingulate cortex, and brain stem, which was confirmed by a voxel-wise analysis comparing baseline and post1 ASL measurements and identifying significantly different clusters covering the same brain regions. In addition, we demonstrated CBF recovery in these brain regions for the post2 ASL measurements compared to baseline measurements. For the thalamus, a VOI-based correlation analysis detected a significant correlation between PSL plasma concentration and CBF decrease relative to baseline conditions. DiscussionA pattern of local and dose dependent CBF decrease was demonstrated following PSL administration. More generally, these findings present the potential of simultaneous PET and ASL measurements to follow the time course of drug effects and to differentiate between the efficacy of different drugs in patient groups.

Evaluating whole-brain tissue-property changes in MRI-negative pharmacoresistant focal epilepsies using MR fingerprinting.

We aim to quantify whole-brain tissue-property changes in patients with magnetic resonance imaging (MRI)-negative pharmacoresistant focal epilepsy by three-dimensional (3D) magnetic resonance fingerprinting (MRF). We included 30 patients with pharmacoresistant focal epilepsy and negative MRI by official radiology report, as well as 40 age- and gender-matched healthy controls (HCs). MRF scans were obtained with 1 mm3 isotropic resolution. Quantitative T1 and T2 relaxometry maps were reconstructed from MRF and registered to the Montreal Neurological Institute (MNI) space. A two-sample t test was performed in Functional Magnetic Resonance Imaging of the Brain (FMRIB) Software Library (FSL) to evaluate significant abnormalities in patients comparing to HCs, with correction by the threshold-free cluster enhancement (TFCE) method. Subgroups analyses were performed for extra-temporal epilepsy/temporal epilepsy (ETLE/TLE), and for those with/without subtle abnormalities detected by morphometric analysis program (MAP), to investigate each subgroup's pattern of MRF changes. Correlation analyses were performed between the mean MRF values in each significant cluster and seizure-related clinical variables. Compared to HCs, patients exhibited significant group-level T1 increase ipsilateral to the epileptic origin, in the mesial temporal gray matter (GM) and white matter (WM), temporal pole GM, orbitofrontal GM, hippocampus, and amygdala, with scattered clusters in the neocortical temporal and insular GM. No significant T2 changes were detected. The ETLE subgroup showed a T1-increase pattern similar to the overall cohort, with additional involvement of the ipsilateral anterior cingulate GM. The subgroup of MAP+ patients also showed a T1-increase pattern similar to the overall cohort, with additional cluster in the ipsilateral lateral orbitofrontal GM. Higher T1 was associated with younger seizure-onset age, longer epilepsy duration, and higher seizure frequency. MRF revealed group-level T1 increase in limbic/paralimbic structures ipsilateral to the epileptic origin, in patients with pharmacoresistant focal epilepsy and no apparent lesions on MRI, suggesting that these regions may be commonly affected by seizures in the epileptic brain. The significant association between T1 increase and higher seizure burden may reflect progressive tissue damage.

Review of Template-Based Neuroimaging Tools in Neuro-Oncology: Novel Insights

Background: A common MRI reference space allows for easy communication of findings, and has led to high-impact discoveries in neuroscience. Brain MRI of neuro-oncology patients with mass lesions or surgical cavities can now be accurately transformed into reference space, allowing for a reliable comparison across patients. Despite this, it is currently seldom used in neuro-oncology, leaving analytic tools untapped. The aim of this study was to systematically review the neuro-oncology literature utilizing reference space. Methods: A systematic review of the neuro-oncology publications was conducted according to PRISMA statement guidelines. Studies specially reporting the use of the Montreal Neurological Institute (MNI) reference space were included. Studies were categorized according to their type of input data and their contributions to the field. A sub-analysis focusing on connectomics and transcriptomics was also included. Results: We identified only 101 articles that utilized the MNI brain in neuro-oncology research. Tumor locations (n = 77) and direct electrocortical stimulation (n = 19) were the most common source of data. A majority of studies (n = 51) provided insights on clinical factors such as tumor subtype, growth progression, and prognosis. A small group of studies (n = 21) have used the novel connectomic and transcriptomic tools. Conclusions: Brain MRI of neuro-oncology patients can be accurately transformed to MNI space. This has contributed to enhance our understanding of a wide variety of clinical questions ranging from tumor subtyping to symptom mapping. Many advanced tools such as connectomics and transcriptomics remain relatively untapped, thereby hindering our knowledge of neuro-oncology.

Brain metastases from small cell lung cancer and non-small cell lung cancer: comparison of spatial distribution and identification of metastatic risk regions.

This study aims to investigate the spatial distribution difference of brain metastases (BM) between small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) and to identify the metastatic risk in brain regions. T1-enhanced MR images of 2997 BM from 728 eligible patients with SCLC and NSCLC were retrospectively reviewed by three independent medical institutions in China. All images were spatially normalised according to the Montreal Neurological Institute space, following BM delineation confirmed by three senior radiologists. The brain regions in the normalised images were identified based on the merged Anatomical Automatic Labeling atlas, and all BM locations were mapped onto these brain regions. Two-tailed proportional hypothesis testing was used to compare the BM observed rate with the expected rate based on the region's volume, and metastatic risk regions were finally identified. In SCLC and NSCLC, BM was mainly present in the deep white matter (22.51% and 17.96%, respectively), cerebellar hemisphere (9.84% and 7.46%, respectively) and middle frontal gyrus (6.72% and 7.97%, respectively). The cerebellar hemisphere was a high-risk brain region in the SCLC. The precentral gyrus, middle frontal gyrus, paracentral lobule and cerebellar hemisphere were high-risk BM in the NSCLC. The inferior frontal gyrus and the temporal pole were a low-risk brain region in the SCLC and NSCLC, respectively. The spatial BM distribution between SCLC and NSCLC is similar. Several critical brain regions had relatively low BM frequency in both SCLC and NSCLC, where a low-dose radiation distribution can be delivered due to adequate preoperative evaluations.