Methodological considerations on diffusion MRI tractography in infants aged 0-2 years: a scoping review.

Diffusion MRI (dMRI) enables studying the complex architectural organization of the brain's white matter (WM) through virtual reconstruction of WM fiber tracts (tractography). Despite the anticipated clinical importance of applying tractography to study structural connectivity and tract development during the critical period of rapid infant brain maturation, detailed descriptions on how to approach tractography in young infants are limited. Over the past two decades, tractography from infant dMRI has mainly been applied in research settings and focused on diffusion tensor imaging (DTI). Only few studies used techniques superior to DTI in terms of disentangling information on the brain's organizational complexity, including crossing fibers. While more advanced techniques may enhance our understanding of the intricate processes of normal and abnormal brain development and extensive knowledge has been gained from application on adult scans, their applicability in infants has remained underexplored. This may partially be due to the higher technical requirements versus the need to limit scan time in young infants. We review various previously described methodological practices for tractography in the infant brain (0-2 years-of-age) and provide recommendations to optimize advanced tractography approaches to enable more accurate reconstructions of the brain WM's complexity. IMPACT: Diffusion tensor imaging is the technique most frequently used for fiber tracking in the developing infant brain but is limited in capability to disentangle the complex white matter organization. Advanced tractography techniques allow for reconstruction of crossing fiber bundles to better reflect the brain's complex organization. Yet, they pose practical and technical challenges in the fast developing young infant's brain. Methods on how to approach advanced tractography in the young infant's brain have hardly been described. Based on a literature review, recommendations are provided to optimize tractography for the developing infant brain, aiming to advance early diagnosis and neuroprotective strategies.

Feasibility study to unveil the potential: considerations of constrained spherical deconvolution tractography with unsedated neonatal diffusion brain MRI data.

Purpose: The study aimed to (1) assess the feasibility constrained spherical deconvolution (CSD) tractography to reconstruct crossing fiber bundles with unsedated neonatal diffusion MRI (dMRI), and (2) demonstrate the impact of spatial and angular resolution and processing settings on tractography and derived quantitative measures. Methods: For the purpose of this study, the term-equivalent dMRIs (single-shell b800, and b2000, both 5 b0, and 45 gradient directions) of two moderate-late preterm infants (with and without motion artifacts) from a local cohort [Brain Imaging in Moderate-late Preterm infants (BIMP) study; Calgary, Canada] and one infant from the developing human connectome project with high-quality dMRI (using the b2600 shell, comprising 20 b0 and 128 gradient directions, from the multi-shell dataset) were selected. Diffusion tensor imaging (DTI) and CSD tractography were compared on b800 and b2000 dMRI. Varying image resolution modifications, (pre-)processing and tractography settings were tested to assess their impact on tractography. Each experiment involved visualizing local modeling and tractography for the corpus callosum and corticospinal tracts, and assessment of morphological and diffusion measures. Results: Contrary to DTI, CSD enabled reconstruction of crossing fibers. Tractography was susceptible to image resolution, (pre-) processing and tractography settings. In addition to visual variations, settings were found to affect streamline count, length, and diffusion measures (fractional anisotropy and mean diffusivity). Diffusion measures exhibited variations of up to 23%. Conclusion: Reconstruction of crossing fiber bundles using CSD tractography with unsedated neonatal dMRI data is feasible. Tractography settings affected streamline reconstruction, warranting careful documentation of methods for reproducibility and comparison of cohorts.

Cluster-based analysis of PTSD-Checklist for DSM-5 (PCL-5) in civilians with post-concussive cognitive changes.

OBJECTIVE: This study explores the relationship between PTSD symptoms and cognition in patients with persistent post-concussive symptoms (PPCS). METHODS: Adults with PPCS presenting to a specialized brain injury clinic provided demographic and injury information and completed the PTSD checklist for DSM-5, Generalized Anxiety Disorder Scale-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9). The Montreal Cognitive Assessment (MoCA) was used to screen for possible cognitive concerns. Multiple regression analysis (MLR) adjusting for age, sex, mechanism of injury, psychiatric history, number of previous concussions, months since most recent injury, and mental health questionnaire scores was used to determine associations between PTSD and cognition. Binomial logistic regression explored the relationship between domains of the MoCA and PCL-5 scores. RESULTS: We found a negative correlation between MoCA scores, PCL-5 (ρ=-0.211, p = 0.009) and PHQ-9 (ρ=-0.187, p = 0.021) in patients with PPCS and collinearity of PCL-5 and PHQ-9 scores. Significantly higher Arousal and Reactivity cluster scores within the PCL-5 were associated with poorer scores on naming and abstract tasks on the MoCA. CONCLUSION: The association between specific PCL-5 clusters and lower MoCA scores may represent a viable target for psychotherapeutic and psychopharmacologic intervention in patients with cognitive changes associated with PPCS.

Obsessive-compulsive disorder following severe traumatic brain injury.

Obsessive-compulsive disorder (OCD) as a consequence of severe traumatic brain injury (TBI) has been reported in a limited number of case studies. Informed by CARE guidelines, we present the case of a boy in his late adolescence who sustained a severe TBI from a motor vehicle crash. His injuries required a prolonged stay in the hospital, including 3 weeks in the intensive care unit and a craniotomy to evacuate a large subdural haematoma. Obsessive-compulsive behaviours were first observed on discharge from the hospital and became worse over time. Compulsive behaviours were considered in light of a neuropsychological examination, and a diagnosis of OCD was attained. Sertraline was prescribed and effectively reduced the severity of OCD symptoms. Given the challenges comorbid conditions can pose to neurorehabilitation, a better understanding of patterns in OCD symptoms and brain lesions among reported cases will help guide the diagnosis of OCD among individuals with severe TBI.

Practical Stepwise Approach to Performing Neonatal Brain MR Imaging in the Research Setting.

Magnetic resonance imaging (MRI) is a non-invasive imaging technique that is commonly used for the visualization of newborn infant brains, both for clinical and research purposes. One of the main challenges with scanning newborn infants, particularly when scanning without sedation in a research setting, is movement. Infant movement can affect MR image quality and therewith reliable image assessment and advanced image analysis. Applying a systematic, stepwise approach to MR scanning during the neonatal period, including the use of the feed-and-bundle technique, is effective in reducing infant motion and ensuring high-quality images. We provide recommendations for one such systematic approach, including the step-by-step preparation and infant immobilization, and highlight safety precautions to minimize any potential risks. The recommendations are primarily focused on scanning newborn infants for research purposes but may be used successfully for clinical purposes as well, granted the infant is medically stable. Using the stepwise approach in our local research setting, our success rate of acquiring high-quality, analyzable infant brain MR images during the neonatal period is as high as 91%.

The Effect of Preoperative, Low-Dose Intrathecal Morphine on Patient Outcomes Following Lumbar Fusion Surgery: Can We Teach an Old Dog New Tricks?

BACKGROUND: Early pain control after lumbar fusion presents a challenge to patients and providers. Intrathecal morphine (ITM) has been used at the end of these procedures with limited benefit, but recent data suggest low-dose ITM at case initiation may be effective. This study aims to evaluate the use of preoperative ITM during lumbar fusion to determine whether there is a benefit for these patients. METHODS: One hundred and eighty lumbar fusion patients between 1 January 2018 and 31 May 2022 were evaluated. Patients were grouped by whether they received preoperative, low-dose ITM or not. Outcomes of interest included hospital narcotic consumption, pain scores, opioid-related complications, and complications within the first 90 days. RESULTS: Sixty-five study patients received 200 µg ITM at case initiation and 115 did not. No differences in length of stay, discharge disposition, or complications in the first 90 days were noted. ITM patients received fewer milligram morphine equivalents in the postanesthesia care unit (9.7 ± 31.23 vs 21.83 ± 21.07; P = 0.006) and on postoperative day 0 (18.60 ± 35.47 vs 35.47 ± 28.51; P = 0.001). Pain scores were lower in the ITM group both in the postanesthesia care unit and on postoperative day 0, with a decrease in extreme pain scores (>7; 35.4% vs 53.0%; P = 0.034). CONCLUSIONS: ITM appears to be safe and effective for reducing early pain and narcotic consumption on the day of surgery for lumbar fusion patients and may hold value for incorporation into rapid recovery protocols and for improving pain-related patient satisfaction. CLINICAL RELEVANCE: ITM appears to be safe and effective for reducing early pain and narcotic consumption on the day of surgery for lumbar fusion patients and may hold value for incorporation into rapid recovery protocols and for improving pain-related patient satisfaction.

Factors Associated with Quality of Life in Adults with Persistent Post-Concussion Symptoms.

OBJECTIVE: To assess demographic, clinical, and injury characteristics associated with health-related quality of life (HRQOL) in adults with persistent post-concussion symptoms (PPCS). METHODS: Adults with PPCS presenting to a specialized brain injury clinic completed demographic, injury, and clinical outcome questionnaires at the initial clinic assessment. Clinical outcome measures were collected including the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder Scale-7 (GAD-7), and the Fatigue Severity Scale (FSS). HRQOL was measured using the Quality of Life after Brain Injury (QOLIBRI) questionnaire. Stepwise hierarchical multiple regression analysis adjusting for age, sex, and months since injury was used to determine associations between quality of life and clinical outcome measures. RESULTS: Overall, 125 participants were included. The PHQ-9, FSS, and GAD-7 were significant predictors of QOLIBRI scores (R2 = 0.481, p < .001), indicating that participants with higher levels of depressive symptoms, fatigue, and anxiety reported poorer HRQOL. The PHQ-9 score was the strongest predictor, accounting for 42.0% of the variance in QOLIBRI scores. No demographic or injury characteristics significantly predicted QOLIBRI scores. There was a high prevalence of depressive symptoms with 72.8% of participants having PHQ-9 scores ≥ 10. CONCLUSION: Among patients with PPCS, mental health and fatigue are important contributors to HRQOL. As there is a high burden of mood disorders and fatigue in this population, targeted treatments for these concerns may impact the quality of life.

Early Supported Discharge for Neurorehabilitation Following Acquired Brain Injury.

Introduction: Early Supported Discharge (ESD) is a clinical flow management service offering interdisciplinary rehabilitation, wherein patients are provided supported in-home rehabilitation treatment; in comparison to conventional hospital-based rehabilitation model of service delivery. There has been little research into the functional outcomes for other types of acquired brain injury (ABI). Methods: In this prospective cohort study, ABI patients presenting at a level I trauma center in Calgary, Canada were placed in either an ESD program or conventional inpatient rehabilitation (IPR) program based on their medical history and presentation. A small number of patients completed both programs (ESD+IPR group). ESD therapies were designed to emulate IPR. Participants completed professionally-rated Mayo-Portland Adaptability Index-4 (MPAI), Quality of Life after Brain Injury (QOLIBRI), Generalized Anxiety Questionnaire-7 (GAD7), Montreal Cognitive Assessment (MoCA), and Patient Health Questionnaire-9 (PHQ9) surveys at 1, 3, and 6 months following initial assessment pre-rehabilitation. Caregivers completed the Zarit Burden Interview (ZBI) at the same time points. The Supervision Rating Scale (SRS) and Disability Rating Scale (DRS) were completed at admission to rehabilitation and all follow-ups. Generalized estimate equations models were used to describe the three groups over time, including age as a covariate. Results: Significant effects of time were reported in the MPAI participant sub-score in the ESD and IPR groups ( χ ( 2 ) 2 = 42.429, p < 0.000; χ ( 2 ) 2 = 9.773, p = 0.008), showing significantly higher scores between 1 and 3 month timepoints for both groups. ZBI scores were significantly lower in the ESD group at 1 month compared to 3 and 6 months ( χ ( 2 ) 2 = 31.252, p < 0.001). The proportion of patients with medical complications during rehabilitation was 25.3% in ESD compared to 74.7% patients in IPR. Conclusions: Improvements in functional outcomes were evident in patients participating in ESD and IPR, with more medical complications reported in the IPR group. Caregiver burden lessened over time in the ESD group but not in the IPR group. Both ESD and ESD+IPR groups can be considered viable alternatives to traditional inpatient rehabilitation. A randomized control trial would be required to properly compare rehabilitation streams. Further investigation into affective and lifestyle elements of ABI recovery would also improve our understanding of targeted neurorehabilitation in this population.

Longitudinal Assessment of Cortical Excitability in Children and Adolescents With Mild Traumatic Brain Injury and Persistent Post-concussive Symptoms.

Introduction: Symptoms following a mild traumatic brain injury (mTBI) usually resolve quickly but may persist past 3 months in up to 15% of children. Mechanisms of mTBI recovery are poorly understood, but may involve alterations in cortical neurophysiology. Transcranial Magnetic Stimulation (TMS) can non-invasively investigate such mechanisms, but the time course of neurophysiological changes in mTBI are unknown. Objective/Hypothesis: To determine the relationship between persistent post-concussive symptoms (PPCS) and altered motor cortex neurophysiology over time. Methods: This was a prospective, longitudinal, controlled cohort study comparing children (8-18 years) with mTBI (symptomatic vs. asymptomatic) groups to controls. Cortical excitability was measured using TMS paradigms at 1 and 2 months post injury. The primary outcome was the cortical silent period (cSP). Secondary outcomes included short interval intracortical inhibition (SICI) and facilitation (SICF), and long-interval cortical inhibition (LICI). Generalized linear mixed model analyses were used to evaluate the effect of group and time on neurophysiological parameters. Results: One hundred seven participants (median age 15.1, 57% female) including 78 (73%) with symptomatic PPCS and 29 with asymptomatic mTBI, were compared to 26 controls. Cortical inhibition (cSP and SICI) was reduced in the symptomatic group compared to asymptomatic group and tended to increase over time. Measures of cortical facilitation (SICF and ICF) were increased in the asymptomatic group and decreased over time. TMS was well tolerated with no serious adverse events. Conclusions: TMS-assessed cortical excitability is altered in children following mild TBI and is dependent on recovery trajectory. Our findings support delayed return to contact sports in children even where clinical symptoms have resolved.

Microstructural neuroimaging of white matter tracts in persistent post-concussion syndrome: A prospective controlled cohort study.

INTRODUCTION: Children with mild traumatic brain injury (mTBI) typically recover quickly, however approximately 15% experience persistent post-concussive symptoms (PPCS) past 3 months. The microstructural pathology associated with underlying persistent symptoms is poorly understood but is suggested to involve axonal injury to white matter tracts. Diffusion tensor imaging (DTI) can be used to visualize and characterize damage to white matter microstructure of the brain. OBJECTIVE: We aimed to investigate white matter microstructure in children with persistent concussive symptoms as compared to typically developing controls, alongside evaluating differences in white matter changes over time and how this relates to symptom recovery. METHODS: The current study is a prospective, longitudinal, controlled cohort study of children with mTBI. 104 children aged 8 to 18 years with a mTBI (72 symptomatic; 32 asymptomatic) were recruited from the Alberta Children's Hospital and compared to 20 healthy controls. Microstructural evidence of white matter injury was evaluated using DTI one month post injury and repeated 4 to 6 weeks later. Primary outcomes included fractional anisotropy and mean diffusivity of the corticospinal tracts, uncinate fasciculi, and motor fibers of the corpus callosum. Post-concussive symptoms were also measured using the Post-Concussion Symptom Inventory (PCSI) taken at both time points. RESULTS: Fractional anisotropy of the left uncinate fasciculi was lower in symptomatic children compared to controls (F(2,119) = 3.582, p = 0.031). No other significant differences were observed. CONCLUSIONS: Our findings provide evidence of microstructural injury following mTBI in children with ongoing post-concussive symptoms one month post injury. The changes were persistent 4-6 weeks later. Further longitudinal studies of white matter microstructure in PPCS will be helpful to clarify whether these white matter alterations resolve over time.