A Low-Intensity Transcranial Focused Ultrasound Parameter Exploration Study of the Ventral Capsule/Ventral Striatum.

OBJECTIVES: Deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS) is effective for treatment-resistant obsessive-compulsive disorder (OCD); however, DBS is associated with neurosurgical risks. Transcranial focused ultrasound (tFUS) is a newer form of noninvasive (ie, nonsurgical) stimulation that can modulate deeper regions, such as the VC/VS. tFUS parameters have just begun to be studied and have often not been compared in the same participants. We explored the effects of three VC/VS tFUS protocols and an entorhinal cortex (ErC) tFUS session on the VC/VS and cortico-striato-thalamo-cortical circuit (CSTC) in healthy individuals for later application to patients with OCD. MATERIALS AND METHODS: Twelve individuals participated in a total of 48 sessions of tFUS in this exploratory multisite, within-subject parameter study. We collected resting-state, reward task, and arterial spin-labeled (ASL) magnetic resonance imaging scans before and after ErC tFUS and three VC/VS tFUS sessions with different pulse repetition frequencies (PRFs), pulse widths (PWs), and duty cycles (DCs). RESULTS: VC/VS protocol A (PRF = 10 Hz, PW = 5 ms, 5% DC) was associated with increased putamen activation during a reward task (p = 0.003), and increased VC/VS resting-state functional connectivity (rsFC) with the anterior cingulate cortex (p = 0.022) and orbitofrontal cortex (p = 0.004). VC/VS protocol C (PRF = 125 Hz, PW = 4 ms, 50% DC) was associated with decreased VC/VS rsFC with the putamen (p = 0.017), and increased VC/VS rsFC with the globus pallidus (p = 0.008). VC/VS protocol B (PRF = 125 Hz, PW = 0.4 ms, 5% DC) was not associated with changes in task-related CSTC activation or rsFC. None of the protocols affected CSTC ASL perfusion. CONCLUSIONS: This study began to explore the multidimensional parameter space of an emerging form of noninvasive brain stimulation, tFUS. Our preliminary findings in a small sample suggest that VC/VS tFUS should continue to be investigated for future noninvasive treatment of OCD.

Body size interacts with the structure of the central nervous system: A multi-center in vivo neuroimaging study.

Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subject's sex and age. However, corrections for body size (i.e. height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the importance of body size parameters in their relationship with spinal cord (SC) and brain magnetic resonance imaging (MRI) metrics. Data were derived from a cosmopolitan population of 267 healthy human adults (age 30.1±6.6 years old, 125 females). We show that body height correlated strongly or moderately with brain gray matter (GM) volume, cortical GM volume, total cerebellar volume, brainstem volume, and cross-sectional area (CSA) of cervical SC white matter (CSA-WM; 0.44≤r≤0.62). In comparison, age correlated weakly with cortical GM volume, precentral GM volume, and cortical thickness (-0.21≥r≥-0.27). Body weight correlated weakly with magnetization transfer ratio in the SC WM, dorsal columns, and lateral corticospinal tracts (-0.20≥r≥-0.23). Body weight further correlated weakly with the mean diffusivity derived from diffusion tensor imaging (DTI) in SC WM (r=-0.20) and dorsal columns (-0.21), but only in males. CSA-WM correlated strongly or moderately with brain volumes (0.39≤r≤0.64), and weakly with precentral gyrus thickness and DTI-based fractional anisotropy in SC dorsal columns and SC lateral corticospinal tracts (-0.22≥r≥-0.25). Linear mixture of sex and age explained 26±10% of data variance in brain volumetry and SC CSA. The amount of explained variance increased at 33±11% when body height was added into the mixture model. Age itself explained only 2±2% of such variance. In conclusion, body size is a significant biological variable. Along with sex and age, body size should therefore be included as a mandatory variable in the design of clinical neuroimaging studies examining SC and brain structure.

Apparent diffusion coefficient values predict response to brachytherapy in bulky cervical cancer.

BACKGROUND: Diffusion-weighted magnetic resonance imaging (DWI) provides a measurement of tumor cellularity. We evaluated the potential of apparent diffusion coefficient (ADC) values obtained from post-external beam radiation therapy (EBRT) DWI and prior to brachytherapy (BT) to predict for complete metabolic response (CMR) in bulky cervical cancer. METHODS: Clinical and DWI (b value = 500 s/mm2) data were obtained from patients undergoing interstitial BT with high-risk clinical target volumes (HR-CTVs) > 30 cc. Volumes were contoured on co-registered T2 weighted images and 90th percentile ADC values were calculated. Patients were stratified by CMR (defined by PET-CT at three months post-BT). Relation of CMR with 90th percentile ADC values and other clinical factors (International Federation of Gynecology and Obstetrics (FIGO) stage, histology, tumor and HR-CTV size, pre-treatment hemoglobin, and age) was assessed both in univariate and multivariate logistic regression analyses. Youden's J statistic was used to identify a threshold value. RESULTS: Among 45 patients, twenty-eight (62%) achieved a CMR. On univariate analysis for CMR, only 90th percentile ADC value was significant (p = 0.029) while other imaging and clinical factors were not. Borderline significant factors were HR-CTV size (p = 0.054) and number of chemotherapy cycles (p = 0.078). On multivariate analysis 90th percentile ADC (p < 0.0001) and HR-CTV size (p < 0.003) were highly significant. Patients with 90th percentile ADC values above 2.10 × 10- 3 mm2/s were 5.33 (95% CI, 1.35-24.4) times more likely to achieve CMR. CONCLUSIONS: Clinical DWI may serve to risk-stratify patients undergoing interstitial BT for bulky cervical cancer.

Sludge-based candidate reference materials for enhanced quality control of particulate processes in total organic carbon analysis for wastewater1.

Accurate analyses of total organic carbon (TOC) encompassing particulate organic carbon in wastewater are key for evaluating the behavior of particulate organic contaminants and maintaining the carbon mass balance throughout the wastewater treatment process. This study was conducted to develop candidate reference materials of environmental origin from excess sludge collected from wastewater treatment facilities, primarily receiving industrial wastewater and livestock manure as the main sources. Homogeneity and stability assessments for total carbon (TC) and TOC were conducted in the particle samples following the standardized procedures of ISO Guide 35 and ISO 13258. The results showed that high inorganic carbon (IC) content in particles, such as YJ(500) (IC: 29%), rendered them unsuitable for TOC quality control (QC), as they increased uncertainty in both homogeneity and stability assessments. Additionally, a13C NMR analysis revealed that samples with a high (O-alkyl)/(C-H-alkyl) ratio in their carbon structures exhibited relatively low stability. Through the homogeneity and stability assessments, a particle sample, YJ(100), was selected as the reference material (RM); the assigned values were as follows: 30.78% for TC and 27.94% for TOC, with uncertainties of 0.01% and 1.1%, respectively. Furthermore, considering sample transportation conditions, the safe storage period for the RM particles was determined to be 2 weeks under harsh conditions (at 40 °C). In our inter-laboratory test (n = 8) using the particle samples, we confirmed that the particle samples can effectively enhance particle processing QC and validate a proposed suspended solids pretreatment method. This study showcases valuable environmental particle sample production and evaluation, offering potential advancements in the QC of TOC analysis for wastewater samples.

Reward learning improves social signal processing in autism model mice.

Social and reward signal processing and their association are critical elements of social motivation. Despite the use of reward learning to improve the social interactions of patients with autism spectrum disorder (ASD), the underlying neural mechanisms are unknown. Here, we found different yet conjunct neuronal representations of social and reward signals in the mouse medial prefrontal cortex (mPFC). We also found that social signal processing is selectively disrupted, whereas reward signal processing is intact in the mPFC of Shank2-knockout mice, a mouse model of ASD. Furthermore, reward learning not only allows Shank2-knockout mice to associate social stimuli with reward availability, but it also rescues the impaired social signal processing. These findings provide insights into the neural basis for the therapeutic use of reward learning in ASD.

A quantitative analysis of spontaneous alternation behaviors on a Y-maze reveals adverse effects of acute social isolation on spatial working memory.

Animals tend to alternate between different choices, which requires the ability to remember recent choices. The Y-maze spontaneous alternation test is widely used in various animal models for assessing short-term memory, and its precise evaluation depends upon the accurate determination of the arm visit sequence. However, an objective method for defining arm visits is lacking owing to uncertainty regarding the extent to which an animal must go into the arm to be considered visited. Here, we conducted quantitative analyses on mice behavior in the Y-maze while systematically varying the arm visit threshold and assessed the effect of acute social isolation on spatial working memory. Our results revealed that 24-h social isolation significantly reduced spontaneous alternation rate when the arm threshold was set at the distal part of the arm. Furthermore, the memory of the recently visited arms faded away faster in the socially isolated mice. However, other behavioral factors were comparable to those of the group-housed mice, indicating a specific impairment of short-term memory. Our findings suggest that the location of arm visit threshold is critical for the precise evaluation of short-term memory, and our study provides a method for comprehensively and systematically assessing spontaneous alternation behavior in the Y-maze.

Predictive values of spinal cord diffusion magnetic resonance imaging to characterize outcomes after contusion injury.

OBJECTIVES: To explore filtered diffusion-weighted imaging (fDWI), in comparison with conventional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI), as a predictor for long-term locomotor and urodynamic (UD) outcomes in Yucatan minipig model of spinal cord injury (SCI). Additionally, electrical conductivity of neural tissue using D-waves above and below the injury was measured to assess correlations between fDWI and D-waves data. METHODS: Eleven minipigs with contusion SCI at T8-T10 level underwent MRI at 3T 4 h. post-SCI. Parameters extracted from region of interest analysis included Daxial from fDWI at injury site, fractional anisotropy and radial diffusivity from DTI above the injury site along with measures of edema length and cord width at injury site from T2 -weighted images. Locomotor recovery was assessed pre- and weekly post-SCI through porcine thoracic injury behavior scale (PTIBS) and UD were performed pre- and at 12 weeks of SCI. D-waves latency and amplitude differences were recorded before and immediately after SCI. RESULTS: Two groups of pigs were found based on the PTIBS at week 12 (p < 0.0001) post-SCI and were labeled "poor" and "good" recovery. D-waves amplitude decreased below injury and increased above injury. UD outcomes pre/post SCI changed significantly. Conventional MRI metrics from T2 -weighted images were significantly correlated with diffusion MRI metrics. Daxial at injury epicenter was diminished by over 50% shortly after SCI, and it differentiated between good and poor locomotor recovery and UD outcomes. INTERPRETATION: Similar to small animal studies, fDWI from acute imaging after SCI is a promising predictor for functional outcomes in large animals.

GPX4 overexpressed non-small cell lung cancer cells are sensitive to RSL3-induced ferroptosis.

Ferroptosis can be induced by inhibiting antioxidant enzymes GPX4 or system Xc-, increased intracellular iron concentrations, and lipid peroxidation. Recently, it has been suggested that ferroptosis can be an effective way to induce cancer cell death, although the specific relevance and mechanism of ferroptosis have not been fully elucidated. Here, we investigated the anticancer effects of ferroptosis inducers erastin and RSL3 on non-small cell lung cancer (NSCLC) cells. RSL3 induced cell death more effectively in NSCLC cells than erastin, with limited cytotoxicity in BEAS-2B normal bronchial epithelial cells. The sensitivity of NSCLC cells to RSL3 induced death was dependent on GPX4 expression levels; the effect of RSL3 was reversed by ferrostatin-1 (a ferroptosis inhibitor) but not by Z-VAD-FMK, chloroquine, bafilomycin A1, or necrostatin-1. RSL3 induced ferroptosis by promoting lipid peroxidation, elevating intracellular LIP concentration and ROS level, and blocking GSH-to-GSSH conversion through the inhibition of GPX4 and induction of Nrf2/HO1. Furthermore, RSL3 induced autophagosomes but disrupted the formation of autolysosomes with lysosomal membrane destabilization. GPX4 knockdown had a similar effect on ferroptosis phenotypes as RSL3. Taken together, RSL3-induced ferroptosis depends on the regulation of GPX4-Nrf2/HO1 in NSCLC cells. These results may be useful in predicting the ferroptosis response in NSCLC as well as drug resistant cancer cells.

Identification of the cause of the difference among TOC quantitative methods according to the water sample characteristics.

Total organic carbon (TOC) analysis with accurate determination of particulate organic carbon (POC) content in suspended solids (SS) containing water is critical for evaluating the environmental impact of particulate organic pollutants in water and calculating the carbon cycle mass balance. TOC analysis is divided into the non-purgeable organic carbon (NPOC) and differential (known as TC-TIC) methods; although the selection of method is greatly affected by the sample matrix characteristics of SS, no studies have investigated this. This study quantitatively evaluates the effect of SS containing inorganic carbon (IC) and purgeable organic carbon (PuOC), as well as that of sample pretreatment, on the accuracy and precision of TOC measurement in both methods for various environmental water sample types (12 wastewater influents and effluents and 12 types of stream water). For influent and stream water with high SS, the TC-TIC method expressed 110-200 % higher TOC recovery than that for the NPOC method due to POC component losses in SS owing to its conversion into PuOC during sample pretreatment (using ultrasonic) and subsequent loss in the NPOC purging process. Correlation analysis confirmed that particulated organic matter (POM, mg/L) content in SS directly affected this difference (r > 0.74, p < 0.01, n = 24); for POC water samples (those containing >10 mg/L of POM) featuring purgeable dissolved organic matter, TC-TIC was appropriate in securing TOC measurement accuracy. In constrast, in effluent and stream water with low SS (i.e., < ∼5 mg/L) and high IC (> 70 %) contents, the TOC measurement ratios (TC-TIC/NPOC) of both methods were similar, between 0.96 and 1.08, suggesting that NPOC is appropriate for improving precision. Our results provide useful basic data to establish the most reliable TOC analysis method considering SS contents and its properties along with the matrix characteristics of the sample.

Neural function underlying reward expectancy and attainment in adolescents with diverse psychiatric symptoms.

Reward dysfunction has been hypothesized to play a key role in the development of psychiatric conditions during adolescence. To help capture the complexity of reward function in youth, we used the Reward Flanker fMRI Task, which enabled us to examine neural activity during expectancy and attainment of both certain and uncertain rewards. Participants were 84 psychotropic-medication-free adolescents, including 67 with diverse psychiatric conditions and 17 healthy controls. Functional MRI used high-resolution acquisition and high-fidelity processing techniques modeled after the Human Connectome Project. Analyses examined neural activation during reward expectancy and attainment, and their associations with clinical measures of depression, anxiety, and anhedonia severity, with results controlled for family-wise errors using non-parametric permutation tests. As anticipated, reward expectancy activated regions within the fronto-striatal reward network, thalamus, occipital lobe, superior parietal lobule, temporoparietal junction, and cerebellum. Unexpectedly, however, reward attainment was marked by widespread deactivation in many of these same regions, which we further explored using cosine similarity analysis. Across all subjects, striatum and thalamus activation during reward expectancy negatively correlated with anxiety severity, while activation in numerous cortical and subcortical regions during reward attainment positively correlated with both anxiety and depression severity. These findings highlight the complexity and dynamic nature of neural reward processing in youth.

Prefrontal-habenular microstructural impairments in human cocaine and heroin addiction.

The habenula (Hb) is central to adaptive reward- and aversion-driven behaviors, comprising a hub for higher-order processing networks involving the prefrontal cortex (PFC). Despite an established role in preclinical models of cocaine addiction, the translational significance of the Hb and its connectivity with the PFC in humans is unclear. Using diffusion tractography, we detailed PFC structural connectivity with the Hb and two control regions, quantifying tract-specific microstructural features in healthy and cocaine-addicted individuals. White matter was uniquely impaired in PFC-Hb projections in both short-term abstainers and current cocaine users. Abnormalities in this tract further generalized to an independent sample of heroin-addicted individuals and were associated, in an exploratory analysis, with earlier onset of drug use across the addiction subgroups, potentially serving as a predisposing marker amenable for early intervention. Importantly, these findings contextualize a plausible PFC-Hb circuit in the human brain, supporting preclinical evidence for its impairment in cocaine addiction.

Comparison of multicenter MRI protocols for visualizing the spinal cord gray matter.

PURPOSE: Spinal cord gray-matter imaging is valuable for a number of applications, but remains challenging. The purpose of this work was to compare various MRI protocols at 1.5 T, 3 T, and 7 T for visualizing the gray matter. METHODS: In vivo data of the cervical spinal cord were collected from nine different imaging centers. Data processing consisted of automatically segmenting the spinal cord and its gray matter and co-registering back-to-back scans. We computed the SNR using two methods (SNR_single using a single scan and SNR_diff using the difference between back-to-back scans) and the white/gray matter contrast-to-noise ratio per unit time. Synthetic phantom data were generated to evaluate the metrics performance. Experienced radiologists qualitatively scored the images. We ran the same processing on an open-access multicenter data set of the spinal cord MRI (N = 267 participants). RESULTS: Qualitative assessments indicated comparable image quality for 3T and 7T scans. Spatial resolution was higher at higher field strength, and image quality at 1.5 T was found to be moderate to low. The proposed quantitative metrics were found to be robust to underlying changes to the SNR and contrast; however, the SNR_single method lacked accuracy when there were excessive partial-volume effects. CONCLUSION: We propose quality assessment criteria and metrics for gray-matter visualization and apply them to different protocols. The proposed criteria and metrics, the analyzed protocols, and our open-source code can serve as a benchmark for future optimization of spinal cord gray-matter imaging protocols.

Decoding Neural Activity in Sulcal and White Matter Areas of the Brain to Accurately Predict Individual Finger Movement and Tactile Stimuli of the Human Hand.

Millions of people worldwide suffer motor or sensory impairment due to stroke, spinal cord injury, multiple sclerosis, traumatic brain injury, diabetes, and motor neuron diseases such as ALS (amyotrophic lateral sclerosis). A brain-computer interface (BCI), which links the brain directly to a computer, offers a new way to study the brain and potentially restore impairments in patients living with these debilitating conditions. One of the challenges currently facing BCI technology, however, is to minimize surgical risk while maintaining efficacy. Minimally invasive techniques, such as stereoelectroencephalography (SEEG) have become more widely used in clinical applications in epilepsy patients since they can lead to fewer complications. SEEG depth electrodes also give access to sulcal and white matter areas of the brain but have not been widely studied in brain-computer interfaces. Here we show the first demonstration of decoding sulcal and subcortical activity related to both movement and tactile sensation in the human hand. Furthermore, we have compared decoding performance in SEEG-based depth recordings versus those obtained with electrocorticography electrodes (ECoG) placed on gyri. Initial poor decoding performance and the observation that most neural modulation patterns varied in amplitude trial-to-trial and were transient (significantly shorter than the sustained finger movements studied), led to the development of a feature selection method based on a repeatability metric using temporal correlation. An algorithm based on temporal correlation was developed to isolate features that consistently repeated (required for accurate decoding) and possessed information content related to movement or touch-related stimuli. We subsequently used these features, along with deep learning methods, to automatically classify various motor and sensory events for individual fingers with high accuracy. Repeating features were found in sulcal, gyral, and white matter areas and were predominantly phasic or phasic-tonic across a wide frequency range for both HD (high density) ECoG and SEEG recordings. These findings motivated the use of long short-term memory (LSTM) recurrent neural networks (RNNs) which are well-suited to handling transient input features. Combining temporal correlation-based feature selection with LSTM yielded decoding accuracies of up to 92.04 ± 1.51% for hand movements, up to 91.69 ± 0.49% for individual finger movements, and up to 83.49 ± 0.72% for focal tactile stimuli to individual finger pads while using a relatively small number of SEEG electrodes. These findings may lead to a new class of minimally invasive brain-computer interface systems in the future, increasing its applicability to a wide variety of conditions.

Pastable, Adhesive, Injectable, Nanofibrous, and Tunable (PAINT) Biphasic Hybrid Matrices as Versatile Therapeutic Carriers.

A critical challenge in many pharmaceutical fields is developing versatile adjuvant devices that can reduce the off-target delivery of therapeutic materials to target lesions. Herein, a biphasic hybrid fibrous system that can manipulate the spatial and temporal delivery of various therapeutic agents to target lesions by integrating multiple distinct systems and technologies such as fluffy coaxial electrospun polycaprolactone (PCL)/polystyrene (PS) fibers, cyclohexane-mediated leaching to remove PS layers selectively, amine display on PCL fibers, conjugation of naturally occurring adhesive gallol molecules onto hyaluronic acid (HA-g), and electrostatically complexing the aminated PCL fibers with the gallol-conjugated HA. In the context of "paintable" systems on target lesions, the resulting system is called a PAINT matrix (abbreviated according to the initial letter of its features: pastable, adhesive, injectable, nanofibrous, and tunable). Its viscoelastic property, which was attributed by coalescing aminated PCL fibers with viscous HA-g, enabled it to be noninvasively injected and fit into any cavity in the body with various morphologies, manually pasted on tissue surfaces, and adhered onto moisture-rich surfaces to ensure the secure delivery of therapeutics toward the target lesions. The PAINT matrix efficiently supplied immunomodulatory human neural stem cells (hNSCs) at rat hemisectioned spinal cord injury (SCI) sites and promoted both locomotive and sensory recovery in SCI models, presumably by protecting hNSCs against host immunosurveillance. The PAINT matrix will be broadly utilized for efficiently delivering therapeutics to difficult-to-reach target lesions by direct infusion or conventional biomaterial-mediated approaches due to their locations, wet surfaces, or complicated ambient environments.

Evoking highly focal percepts in the fingertips through targeted stimulation of sulcal regions of the brain for sensory restoration.

BACKGROUND: Paralysis and neuropathy, affecting millions of people worldwide, can be accompanied by significant loss of somatosensation. With tactile sensation being central to achieving dexterous movement, brain-computer interface (BCI) researchers have used intracortical and cortical surface electrical stimulation to restore somatotopically-relevant sensation to the hand. However, these approaches are restricted to stimulating the gyral areas of the brain. Since representation of distal regions of the hand extends into the sulcal regions of human primary somatosensory cortex (S1), it has been challenging to evoke sensory percepts localized to the fingertips. OBJECTIVE/HYPOTHESIS: Targeted stimulation of sulcal regions of S1, using stereoelectroencephalography (SEEG) depth electrodes, can evoke focal sensory percepts in the fingertips. METHODS: Two participants with intractable epilepsy received cortical stimulation both at the gyri via high-density electrocorticography (HD-ECoG) grids and in the sulci via SEEG depth electrode leads. We characterized the evoked sensory percepts localized to the hand. RESULTS: We show that highly focal percepts can be evoked in the fingertips of the hand through sulcal stimulation. fMRI, myelin content, and cortical thickness maps from the Human Connectome Project elucidated specific cortical areas and sub-regions within S1 that evoked these focal percepts. Within-participant comparisons showed that percepts evoked by sulcal stimulation via SEEG electrodes were significantly more focal (80% less area; p = 0.02) and localized to the fingertips more often, than by gyral stimulation via HD-ECoG electrodes. Finally, sulcal locations with consistent modulation of high-frequency neural activity during mechanical tactile stimulation of the fingertips showed the same somatotopic correspondence as cortical stimulation. CONCLUSIONS: Our findings indicate minimally invasive sulcal stimulation via SEEG electrodes could be a clinically viable approach to restoring sensation.

Angiogenic gene networks are dysregulated in opioid use disorder: evidence from multi-omics and imaging of postmortem human brain.

Opioid use disorder (OUD) is a public health crisis in the U.S. that causes over 50 thousand deaths annually due to overdose. Using next-generation RNA sequencing and proteomics techniques, we identified 394 differentially expressed (DE) coding and long noncoding (lnc) RNAs as well as 213 DE proteins in Brodmann Area 9 of OUD subjects. The RNA and protein changes converged on pro-angiogenic gene networks and cytokine signaling pathways. Four genes (LGALS3, SLC2A1, PCLD1, and VAMP1) were dysregulated in both RNA and protein. Dissecting these DE genes and networks, we found cell type-specific effects with enrichment in astrocyte, endothelial, and microglia correlated genes. Weighted-genome correlation network analysis (WGCNA) revealed cell-type correlated networks including an astrocytic/endothelial/microglia network involved in angiogenic cytokine signaling as well as a neuronal network involved in synaptic vesicle formation. In addition, using ex vivo magnetic resonance imaging, we identified increased vascularization in postmortem brains from a subset of subjects with OUD. This is the first study integrating dysregulation of angiogenic gene networks in OUD with qualitative imaging evidence of hypervascularization in postmortem brain. Understanding the neurovascular effects of OUD is critical in this time of widespread opioid use.

Open-access quantitative MRI data of the spinal cord and reproducibility across participants, sites and manufacturers.

In a companion paper by Cohen-Adad et al. we introduce the spine generic quantitative MRI protocol that provides valuable metrics for assessing spinal cord macrostructural and microstructural integrity. This protocol was used to acquire a single subject dataset across 19 centers and a multi-subject dataset across 42 centers (for a total of 260 participants), spanning the three main MRI manufacturers: GE, Philips and Siemens. Both datasets are publicly available via git-annex. Data were analysed using the Spinal Cord Toolbox to produce normative values as well as inter/intra-site and inter/intra-manufacturer statistics. Reproducibility for the spine generic protocol was high across sites and manufacturers, with an average inter-site coefficient of variation of less than 5% for all the metrics. Full documentation and results can be found at https://spine-generic.rtfd.io/ . The datasets and analysis pipeline will help pave the way towards accessible and reproducible quantitative MRI in the spinal cord.

Generic acquisition protocol for quantitative MRI of the spinal cord.

Quantitative spinal cord (SC) magnetic resonance imaging (MRI) presents many challenges, including a lack of standardized imaging protocols. Here we present a prospectively harmonized quantitative MRI protocol, which we refer to as the spine generic protocol, for users of 3T MRI systems from the three main manufacturers: GE, Philips and Siemens. The protocol provides guidance for assessing SC macrostructural and microstructural integrity: T1-weighted and T2-weighted imaging for SC cross-sectional area computation, multi-echo gradient echo for gray matter cross-sectional area, and magnetization transfer and diffusion weighted imaging for assessing white matter microstructure. In a companion paper from the same authors, the spine generic protocol was used to acquire data across 42 centers in 260 healthy subjects. The key details of the spine generic protocol are also available in an open-access document that can be found at https://github.com/spine-generic/protocols . The protocol will serve as a starting point for researchers and clinicians implementing new SC imaging initiatives so that, in the future, inclusion of the SC in neuroimaging protocols will be more common. The protocol could be implemented by any trained MR technician or by a researcher/clinician familiar with MRI acquisition.