Sounding out the dynamics: a concise review of high-speed photoacoustic microscopy.

Significance: Photoacoustic microscopy (PAM) offers advantages in high-resolution and high-contrast imaging of biomedical chromophores. The speed of imaging is critical for leveraging these benefits in both preclinical and clinical settings. Ongoing technological innovations have substantially boosted PAM's imaging speed, enabling real-time monitoring of dynamic biological processes. Aim: This concise review synthesizes historical context and current advancements in high-speed PAM, with an emphasis on developments enabled by ultrafast lasers, scanning mechanisms, and advanced imaging processing methods. Approach: We examine cutting-edge innovations across multiple facets of PAM, including light sources, scanning and detection systems, and computational techniques and explore their representative applications in biomedical research. Results: This work delineates the challenges that persist in achieving optimal high-speed PAM performance and forecasts its prospective impact on biomedical imaging. Conclusions: Recognizing the current limitations, breaking through the drawbacks, and adopting the optimal combination of each technology will lead to the realization of ultimate high-speed PAM for both fundamental research and clinical translation.

Childhood development of brain white matter myelin: a longitudinal T1w/T2w-ratio study.

Myelination of human brain white matter (WM) continues into adulthood following birth, facilitating connection within and between brain networks. In vivo MRI studies using diffusion weighted imaging (DWI) suggest microstructural properties of brain WM increase over childhood and adolescence. Although DWI metrics, such as fractional anisotropy (FA), could reflect axonal myelination, they are not specific to myelin and could also represent other elements of WM microstructure, for example, fibre architecture, axon diameter and cell swelling. Little work exists specifically examining myelin development. The T1w/T2w ratio approach offers an alternative non-invasive method of estimating brain myelin. The approach uses MRI scans that are routinely part of clinical imaging and only require short acquisition times. Using T1w/T2w ratio maps from three waves of the Neuroimaging of the Children's Attention Project (NICAP) [N = 95 (208 scans); 44% female; ages 9.5-14.20 years] we aimed to investigate the developmental trajectories of brain white matter myelin in children as they enter adolescence. We also aimed to investigate whether longitudinal changes in myelination of brain WM differs between biological sex. Longitudinal regression modelling suggested non-linear increases in WM myelin brain wide. A positive parabolic, or U-shaped developmental trajectory was seen across 69 of 71 WM tracts modelled. At a corrected level, no significant effect for sex was found. These findings build on previous brain development research by suggesting that increases in brain WM microstructure from childhood to adolescence could be attributed to increases in myelin.

The relationship between cognition and white matter tract damage after mild traumatic brain injury in a premorbidly healthy, hospitalised adult cohort during the post-acute period.

Introduction: Recent developments in neuroimaging techniques enable increasingly sensitive consideration of the cognitive impact of damage to white matter tract (WMT) microstructural organisation after mild traumatic brain injury (mTBI). Objective: This study investigated the relationship between WMT microstructural properties and cognitive performance. Participants setting and design: Using an observational design, a group of 26 premorbidly healthy adults with mTBI and a group of 20 premorbidly healthy trauma control (TC) participants who were well-matched on age, sex, premorbid functioning and a range of physical, psychological and trauma-related variables, were recruited following hospital admission for traumatic injury. Main measures: All participants underwent comprehensive unblinded neuropsychological examination and structural neuroimaging as outpatients 6-10 weeks after injury. Neuropsychological examination included measures of speed of processing, attention, memory, executive function, affective state, pain, fatigue and self-reported outcome. The WMT microstructural properties were estimated using both diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) modelling techniques. Tract properties were compared between the corpus callosum, inferior longitudinal fasciculus, uncinate fasciculus, anterior corona radiata and three segmented sections of the superior longitudinal fasciculus. Results: For the TC group, in all investigated tracts, with the exception of the uncinate fasciculus, two DTI metrics (fractional anisotropy and apparent diffusion coefficient) and one NODDI metric (intra-cellular volume fraction) revealed expected predictive linear relationships between extent of WMT microstructural organisation and processing speed, memory and executive function. The mTBI group showed a strikingly different pattern relative to the TC group, with no relationships evident between WMT microstructural organisation and cognition on most tracts. Conclusion: These findings indicate that the predictive relationship that normally exists in adults between WMT microstructural organisation and cognition, is significantly disrupted 6-10 weeks after mTBI and suggests that WMT microstructural organisation and cognitive function have disparate recovery trajectories.

Association of Acute Infarct Topography With Development of Cerebral Palsy and Neurologic Impairment in Neonates With Stroke.

BACKGROUND AND OBJECTIVES: Research investigating neonatal arterial ischemic stroke (NAIS) outcomes have shown that combined cortical and basal ganglia infarction or involvement of the corticospinal tract predict cerebral palsy (CP). The research question was whether voxel-based lesion-symptom mapping (VLSM) on acute MRI can identify brain regions associated with CP and neurodevelopmental impairments in NAIS. METHODS: Newborns were recruited from prospective Australian and Swiss pediatric stroke registries. CP diagnosis was based on clinical examination. Language and cognitive-behavioral impairments were assessed using the Pediatric Stroke Outcome Measure, dichotomized to good (0-0.5) or poor (≥1), at ≥18 months of age. Infarcts were manually segmented using diffusion-weighted imaging, registered to a neonatal-specific brain template. VLSM was conducted using MATLAB SPM12 toolbox. A general linear model was used to correlate lesion masks with motor, language, and cognitive-behavioral outcomes. Voxel-wise t-statistics were calculated, correcting for multiple comparisons using family-wise error (FWE) rate. RESULTS: Eighty-five newborns met the inclusion criteria. Infarct lateralization was left hemisphere (62%), right (8%), and bilateral (30%). At a median age of 2.1 years (interquartile range 1.9-2.6), 33% developed CP and 42% had neurologic impairments. Fifty-four grey and white matter regions correlated with CP (t > 4.33; FWE < 0.05), including primary motor pathway regions, such as the precentral gyrus, and cerebral peduncle, and regions functionally connected to the primary motor pathway, such as the pallidum, and corpus callosum motor segment. No significant correlations were found for language or cognitive-behavioral outcomes. DISCUSSION: CP after NAIS correlates with infarct regions directly involved in motor control and in functionally connected regions. Areas associated with language or cognitive-behavioral impairment are less clear.

Health care resource utilization and costs among patients with multiple myeloma with exposure to double-class or triple-class multiple myeloma treatments: A retrospective US claims database analysis.

BACKGROUND: Despite recent advancements in the therapeutic landscape, multiple myeloma (MM) remains incurable. There are multiple treatment options available with a novel mechanism of action, but there is limited evidence describing the economic burden among patients with MM exposed to different drug classes and combinations and across different health care settings. OBJECTIVE: To describe all-cause and MM-related health care resource utilization (HCRU) and costs among patients with MM exposed to different drug classes and combinations (ie, double-class and triple-class-exposed) and characterize the economic burden in different health care settings among these patients with MM. METHODS: We conducted a retrospective cohort study using the IBM MarketScan databases. The study included adult patients (aged ≥18 years) diagnosed with MM between December 1, 2015, and December 31, 2019. The study sample comprised double-class-exposed (DCE) and triple-class-exposed (TCE) cohorts, categorized based on their earliest exposure to different combinations of immunomodulatory drugs, proteasome inhibitors, or targeted monoclonal antibody. Patients with at least 1 subsequent line of therapy following the categorization were included, and the start date of the first subsequent line of therapy was the index date. The primary outcomes were all-cause and MM-related HCRU and costs during the follow-up period. Costs were stratified across 8 care settings defined by place of service. The Kaplan-Meier sample average technique was used to estimate the cumulative mean outcomes, accounting for differential follow-up periods. The outcomes were reported as per patient per month (PPPM). 18 years) diagnosed with MM between December 1, 2015, and December 31, 2019. The study sample comprised double-class-exposed (DCE) and triple-class-exposed (TCE) cohorts, categorized based on their earliest exposure to different combinations of immunomodulatory drugs, proteasome inhibitors, or targeted monoclonal antibody. Patients with at least 1 subsequent line of therapy following the categorization were included, and the start date of the first subsequent line of therapy was the index date. The primary outcomes were all-cause and MM-related HCRU and costs during the follow-up period. Costs were stratified across 8 care settings defined by place of service. The Kaplan-Meier sample average technique was used to estimate the cumulative mean outcomes, accounting for differential follow-up periods. The outcomes were reported as per patient per month (PPPM). RESULTS: The study included 1,521 patients with MM, of whom 1,016 (66.8%) were DCE and 505 (33.2%) were TCE. The mean total all-cause health care costs were $20,338 PPPM, and approximately 85% of the total all-cause costs were MM-related. The mean all-cause and MM-related total costs were driven by overall drug costs primarily attributed to MM treatment and administration costs. The TCE cohort was associated with more HCRU and incurred higher costs than the DCE cohort across all categories. The hospital-based ambulatory setting had the highest all-cause and MM-related costs during the follow-up period: $7,302 (95% CI = $6,801-$7,784) PPPM and $6,695 (95% CI = $6,239-$7,136) PPPM, respectively. CONCLUSIONS: The study findings suggest that the economic burden following exposure to multiple drug classes and combinations is substantial, especially among the TCE cohort and in the ambulatory setting. These findings highlight the need for more effective treatments that can mitigate the economic burden of patients with MM. Future research on the HCRU and costs related to recently approved MM treatments with novel mechanisms is warranted. DISCLOSURES: At the time of this study, Dr Yang was a postdoctoral fellow and the fellowship was supported by GSK. Dr Boytsov is a full-time employee of GSK. Dr Carlson discloses consulting fees from Pfizer, AbbVie, and Genentech. Dr Barthold reports no disclosures.

Intracoronary Imaging and Physiology to Guide PCI: Are We Ready for a Class I Guideline Recommendation?

PURPOSE OF REVIEW: Over the last decade, there has been a plethora of evidence to support the utilization of intravascular coronary imaging and physiological assessment to guide percutaneous coronary interventions (PCI). While there is a class I recommendation for the use of coronary physiology to guide PCI, the use of intravascular coronary imaging remains a class IIa recommendation. Herein, we aimed to review the recent scientific evidence from major trials highlighting the consideration for a future class I guideline recommendation for the use of intracoronary imaging. RECENT FINDINGS: The benefits of intravascular ultrasound (IVUS) and optical coherence tomography (OCT) to guide and optimize PCI have been demonstrated in several large trials. These trials have demonstrated that IVUS reduces major adverse cardiovascular events. Similarly, intracoronary physiology has been demonstrated to be an important tool to guide revascularization decision-making and been associated with a lower incidence of death, non-fatal myocardial infarction, and repeat revascularization compared with angiography alone. With existing clinical outcomes data on the benefit of intracoronary physiology and imaging-guided PCI as well as forthcoming data from ongoing trials regarding the use of these modalities, the interventional cardiology community is bound to transition from routine PCI to precision-, image-, and physiology-guided PCI.

Cerebral microhaemorrhage count is related to processing speed, but not level of symptom reporting, independently of age, psychological status and premorbid functioning, after first-ever mild traumatic brain injury.

Cerebral microhaemorrhage is a commonly identified neuropathological consequence of mild traumatic brain injury (mTBI) and can be identified in vivo using susceptibility weighted imaging (SWI). This study aimed to determine whether SWI-detected microhaemorrhages are more common in individuals after a single, first-ever, mTBI event relative to trauma controls (TC) and to investigate whether a linear relationship exists between microhaemorrhage numbers and cognition or symptom reporting in the post-acute period after injury, independently of age, psychological status and premorbid level of functioning. Microhaemorrhagic lesions were identified by expert clinical examination of SWI for 78 premorbidly healthy adult participants who were admitted to hospital after a traumatic injury and had suffered a first-ever mTBI (n = 47) or no head strike (n = 31). Participants underwent objective cognitive examination of processing speed, attention, memory, and executive function as well as self-reported post-concussion symptomatology. Bootstrapping analyses were used as data were not normally distributed. Analyses revealed that the mTBI group had significantly more microhaemorrhages than the TC group (Cohen's d = 0.559). These lesions were only evident in 28% of individuals. The mTBI participants demonstrated a significant linear association between number of microhaemorrhages and processing speed, independently of age, psychological status, or premorbid level of functioning. This study shows that a single mTBI causes cerebral microhaemorrhages to occur in a minority of premorbidly healthy individuals. Greater microhaemorrhage count is independently associated with slower processing speed, but not symptom reporting, during the post-acute injury period.

Exercise as therapy for neurodevelopmental and cognitive dysfunction in people with a Fontan circulation: A narrative review.

People with a Fontan circulation are at risk of neurodevelopmental delay and disability, and cognitive dysfunction, that has significant implications for academic and occupational attainment, psychosocial functioning, and overall quality of life. Interventions for improving these outcomes are lacking. This review article discusses current intervention practices and explores the evidence supporting exercise as a potential intervention for improving cognitive functioning in people living with a Fontan circulation. Proposed pathophysiological mechanisms underpinning these associations are discussed in the context of Fontan physiology and avenues for future research are recommended.

Long-lasting effects of very preterm birth on brain structure in adulthood: A systematic review and meta-analysis.

Early life experiences, such as very preterm (VP) birth, can affect brain and cognitive development. Several prior studies investigated brain structure in adults born VP; synthesising these studies may help to provide a clearer understanding of long-term effects of VP birth on the brain. We systematically searched Medline and Embase for articles that investigated brain structure using MRI in adulthood in individuals born VP (<32 weeks' gestation) or with very low birth weight (VLBW; <1500 g), and controls born at term or with normal birth weight. In total, 77 studies met the review inclusion criteria, of which 28 studies were eligible for meta-analyses, including data from up to 797 VP/VLBW participants and 518 controls, aged 18-33 years. VP/VLBW adults exhibited volumetric, morphologic and microstructural alterations in subcortical and temporal cortical regions compared with controls, with pooled standardised mean differences up to - 1.0 (95% confidence interval: -1.2, -0.8). This study suggests there is a persisting neurological impact of VP birth, which may provide developmental neurobiological insights for adult cognition in high-risk populations.

Intrinsic and secondary epileptogenicity in focal cortical dysplasia type II.

OBJECTIVE: Favorable seizure outcome is reported following resection of bottom-of-sulcus dysplasia (BOSD). We assessed the distribution of epileptogenicity and dysplasia in and around BOSD to better understand this clinical outcome and the optimal surgical approach. METHODS: We studied 27 children and adolescents with magnetic resonance imaging (MRI)-positive BOSD who underwent epilepsy surgery; 85% became seizure-free postresection (median = 5.0 years follow-up). All patients had resection of the dysplastic sulcus, and 11 had additional resection of the gyral crown (GC) or adjacent gyri (AG). Markers of epileptogenicity were relative cortical hypometabolism on preoperative 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET), and spiking, ripples, fast ripples, spike-high-frequency oscillation cross-rate, and phase amplitude coupling (PAC) on preresection and postresection electrocorticography (ECoG), all analyzed at the bottom-of-sulcus (BOS), top-of-sulcus (TOS), GC, and AG. Markers of dysplasia were increased cortical thickness on preoperative MRI, and dysmorphic neuron density and variant allele frequency of somatic MTOR mutations in resected tissue, analyzed at similar locations. RESULTS: Relative cortical metabolism was significantly reduced and ECoG markers were significantly increased at the BOS compared to other regions. Apart from spiking and PAC, which were greater at the TOS compared to the GC, there were no significant differences in PET and other ECoG markers between the TOS, GC, and AG, suggesting a cutoff of epileptogenicity at the TOS rather than a tapering gradient on the cortical surface. MRI and tissue markers of dysplasia were all maximal in the BOS, reduced in the TOS, and mostly absent in the GC. Spiking and PAC reduced significantly over the GC after resection of the dysplastic sulcus. SIGNIFICANCE: These findings support the concept that dysplasia and intrinsic epileptogenicity are mostly limited to the dysplastic sulcus in BOSD and support resection or ablation confined to the MRI-visible lesion as a first-line surgical approach. 18 F-FDG PET and ECoG abnormalities in surrounding cortex seem to be secondary phenomena.

Karawun: a software package for assisting evaluation of advances in multimodal imaging for neurosurgical planning and intraoperative neuronavigation.

PURPOSE: The neuroimaging research community-which includes a broad range of scientific, medical, statistical, and engineering disciplines-has developed many tools to advance our knowledge of brain structure, function, development, aging, and disease. Past research efforts have clearly shaped clinical practice. However, translation of new methodologies into clinical practice is challenging. Anything that can reduce these barriers has the potential to improve the rate at which research outcomes can contribute to clinical practice. In this article, we introduce Karawun, a file format conversion tool, that has become a key part of our work in translating advances in diffusion imaging acquisition and analysis into neurosurgical practice at our institution. METHODS: Karawun links analysis workflows created using open-source neuroimaging software, to Brainlab (Brainlab AG, Munich, Germany), a commercially available surgical planning and navigation suite. Karawun achieves this using DICOM standards supporting representation of 3D structures, including tractography streamlines, and thus offers far more than traditional screenshot or color overlay approaches. RESULTS: We show that neurosurgical planning data, created from multimodal imaging data using analysis methods implemented in open-source research software, can be imported into Brainlab. The datasets can be manipulated as if they were created by Brainlab, including 3D visualizations of white matter tracts and other objects. CONCLUSION: Clinicians can explore and interact with the results of research neuroimaging pipelines using familiar tools within their standard clinical workflow, understand the impact of the new methods on their practice and provide feedback to methods developers. This capability has been important to the translation of advanced analysis techniques into practice at our institution.

A diffusion MRI study of brain white matter microstructure in adolescents and adults with a Fontan circulation: Investigating associations with resting and peak exercise oxygen saturations and cognition.

INTRODUCTION: Adolescents and adults with a Fontan circulation are at risk of cognitive dysfunction; Attention and processing speed are notable areas of concern. Underlying mechanisms and brain alterations associated with worse long-term cognitive outcomes are not well determined. This study investigated brain white matter microstructure in adolescents and adults with a Fontan circulation and associations with resting and peak exercise oxygen saturations (SaO2), predicted maximal oxygen uptake during exercise (% pred VO2), and attention and processing speed. METHODS: Ninety-two participants with a Fontan circulation (aged 13-49 years, ≥5 years post-Fontan completion) had diffusion MRI. Averaged tract-wise diffusion tensor imaging (DTI) metrics were generated for 34 white matter tracts of interest. Resting and peak exercise SaO2 and % pred VO2 were measured during cardiopulmonary exercise testing (CPET; N = 81). Attention and processing speed were assessed using Cogstate (N = 67 and 70, respectively). Linear regression analyses adjusted for age, sex, and intracranial volume were performed to investigate associations between i) tract-specific DTI metrics and CPET variables, and ii) tract-specific DTI metrics and attention and processing speed z-scores. RESULTS: Forty-nine participants were male (53%), mean age was 23.1 years (standard deviation (SD) = 7.8 years). Mean resting and peak exercise SaO2 were 93.1% (SD = 3.6) and 90.1% (SD = 4.7), respectively. Mean attention and processing speed z-scores were -0.63 (SD = 1.07) and -0.72 (SD = 1.44), respectively. Resting SaO2 were positively associated with mean fractional anisotropy (FA) of the left corticospinal tract (CST) and right superior longitudinal fasciculus I (SLF-I) and negatively associated with mean diffusivity (MD) and radial diffusivity (RD) of the right SLF-I (p ≤ 0.01). Peak exercise SaO2 were positively associated with mean FA of the left CST and were negatively associated with mean RD of the left CST, MD of the left frontopontine tract, MD, RD and axial diffusivity (AD) of the right SLF-I, RD of the left SLF-II, MD, RD and AD of the right SLF-II, and MD and RD of the right SLF-III (p ≤ 0.01). Percent predicted VO2 was positively associated with FA of the left uncinate fasciculus (p < 0.01). Negative associations were identified between mean FA of the right arcuate fasciculus, right SLF-II and right SLF-III and processing speed (p ≤ 0.01). No significant associations were identified between DTI-based metrics and attention. CONCLUSION: Chronic hypoxemia may have long-term detrimental impact on white matter microstructure in people living with a Fontan circulation. Paradoxical associations between processing speed and tract-specific DTI metrics could be suggestive of compensatory white matter remodeling. Longitudinal investigations focused on the mechanisms and trajectory of altered white matter microstructure and associated cognitive dysfunction in people with a Fontan circulation are required to better understand causal associations.

Assessment of intraoperative diffusion EPI distortion and its impact on estimation of supratentorial white matter tract positions in pediatric epilepsy surgery.

The effectiveness of correcting diffusion Echo Planar Imaging (EPI) distortion and its impact on tractography reconstruction have not been adequately investigated in the intraoperative MRI setting, particularly for High Angular Resolution Diffusion Imaging (HARDI) acquisition. In this study, we evaluated the effectiveness of EPI distortion correction using 27 legacy intraoperative HARDI datasets over two consecutive surgical time points, acquired without reverse phase-encoded data, from 17 children who underwent epilepsy surgery at our institution. The data was processed with EPI distortion correction using the Synb0-Disco technique (Schilling et al., 2019) and without distortion correction. The corrected and uncorrected b0 diffusion-weighted images (DWI) were first compared visually. The mutual information indices between the original T1-weighted images and the fractional anisotropy images derived from corrected and uncorrected DWI were used to quantify the effect of distortion correction. Sixty-four white matter tracts were segmented from each dataset, using a deep-learning based automated tractography algorithm for the purpose of a standardized and unbiased evaluation. Displacement was calculated between tracts generated before and after distortion correction. The tracts were grouped based on their principal morphological orientations to investigate whether the effects of EPI distortion vary with tract orientation. Group differences in tract distortion were investigated both globally, and regionally with respect to proximity to the resecting lesion in the operative hemisphere. Qualitatively, we observed notable improvement in the corrected diffusion images, over the typically affected brain regions near skull-base air sinuses, and correction of additional distortion unique to intraoperative open cranium images, particularly over the resection site. This improvement was supported quantitatively, as mutual information indices between the FA and T1-weighted images were significantly greater after the correction, compared to before the correction. Maximum tract displacement between the corrected and uncorrected data, was in the range of 7.5 to 10.0 mm, a magnitude that would challenge the safety resection margin typically tolerated for tractography-informed surgical guidance. This was particularly relevant for tracts oriented partially or fully in-line with the acquired diffusion phase-encoded direction. Portions of these tracts passing close to the resection site demonstrated significantly greater magnitude of displacement, compared to portions of tracts remote from the resection site in the operative hemisphere. Our findings have direct clinical implication on the accuracy of intraoperative tractography-informed image guidance and emphasize the need to develop a distortion correction technique with feasible intraoperative processing time.

Biallelic Variants in PYROXD2 Cause a Severe Infantile Metabolic Disorder Affecting Mitochondrial Function.

Pyridine Nucleotide-Disulfide Oxidoreductase Domain 2 (PYROXD2; previously called YueF) is a mitochondrial inner membrane/matrix-residing protein and is reported to regulate mitochondrial function. The clinical importance of PYROXD2 has been unclear, and little is known of the protein's precise biological function. In the present paper, we report biallelic variants in PYROXD2 identified by genome sequencing in a patient with suspected mitochondrial disease. The child presented with acute neurological deterioration, unresponsive episodes, and extreme metabolic acidosis, and received rapid genomic testing. He died shortly after. Magnetic resonance imaging (MRI) brain imaging showed changes resembling Leigh syndrome, one of the more common childhood mitochondrial neurological diseases. Functional studies in patient fibroblasts showed a heightened sensitivity to mitochondrial metabolic stress and increased mitochondrial superoxide levels. Quantitative proteomic analysis demonstrated decreased levels of subunits of the mitochondrial respiratory chain complex I, and both the small and large subunits of the mitochondrial ribosome, suggesting a mitoribosomal defect. Our findings support the critical role of PYROXD2 in human cells, and suggest that the biallelic PYROXD2 variants are associated with mitochondrial dysfunction, and can plausibly explain the child's clinical presentation.

Brain White Matter Development Over the First 13 Years in Very Preterm and Typically Developing Children Based on the T 1-w/T 2-w Ratio.

BACKGROUND AND OBJECTIVES: To investigate brain regional white matter development in full-term (FT) and very preterm (VP) children at term equivalent and 7 and 13 years of age based on the ratio of T 1- and T 2-weighted MRI (T 1-w/T 2-w), including (1) whether longitudinal changes differ between birth groups or sexes, (2) associations with perinatal risk factors in VP children, and (3) relationships with neurodevelopmental outcomes at 13 years. METHODS: Prospective longitudinal cohort study of VP (born <30 weeks' gestation or <1,250 g) and FT infants born between 2001 and 2004 and followed up at term equivalent and 7 and 13 years of age, including MRI studies and neurodevelopmental assessments. T 1-w/T 2-w images were parcellated into 48 white matter regions of interest. RESULTS: Of 224 VP participants and 76 FT participants, 197 VP and 55 FT participants had useable T 1-w/T 2-w data from at least one timepoint. T 1-w/T 2-w values increased between term equivalent and 13 years of age, with little evidence that longitudinal changes varied between birth groups or sexes. VP birth, neonatal brain abnormalities, being small for gestational age, and postnatal infection were associated with reduced regional T 1-w/T 2-w values in childhood and adolescence. Increased T 1-w/T 2-w values across the white matter at 13 years were associated with better motor and working memory function for all children. Within the FT group only, larger increases in T 1-w/T 2-w values from term equivalent to 7 years were associated with poorer attention and executive function, and higher T 1-w/T 2-w values at 7 years were associated with poorer mathematics performance. DISCUSSION: VP birth and multiple known perinatal risk factors are associated with long-term reductions in the T 1-w/T 2-w ratio in white matter regions in childhood and adolescence, which may relate to alterations in microstructure and myelin content. Increased T 1-w/T 2-w ratio at 13 years appeared to be associated with better motor and working memory function and there appeared to be developmental differences between VP and FT children in the associations for attention, executive functioning, and mathematics performance.

Intraoperative magnetic resonance imaging in epilepsy surgery: A systematic review and meta-analysis.

This systematic review investigated the added value of intraoperative magnetic resonance imaging (iMRI)-guidance in epilepsy surgery, compared to conventional non-iMRI surgery, with respect to the rate of gross total resection (GTR), postoperative seizure freedom, neurological deficits, non-neurological complications and reoperations. A comprehensive literature search was conducted using Medline, Embase, PubMed, and Cochrane Reviews databases. Randomized control trials, case control or cohort studies, and surgical case series published from January 1993 to February 2021 that reported on iMRI-guided epilepsy surgery outcomes for either adults or children were eligible for inclusion. Studies comparing iMRI-guided epilepsy surgery to non-iMRI surgery controls were selected for meta-analysis using random-effects models. Forty-two studies matched the selection criteria and were used for qualitative synthesis and ten of these were suitable for meta-analysis. Overall, studies included various 0.2-3.0 Tesla iMRI systems, contained small numbers with heterogenous clinical characteristics, utilized subjective GTR reporting, and had variable follow-up durations. Meta-analysis demonstrated that the use of iMRI-guidance led to statistically significant higher rates of GTR (RR = 1.31 [95% CI = 1.10-1.57]) and seizure freedom (RR = 1.44 [95% CI = 1.12-1.84]), but this was undermined by moderate to significant statistical heterogeneity between studies (I2 = 55% and I2 = 71% respectively). Currently, there is only level III-2 evidence supporting the use of iMRI-guidance over conventional non-iMRI epilepsy surgery, with respect to the studied outcomes.

Automated Perfusion-Diffusion Magnetic Resonance Imaging in Childhood Arterial Ischemic Stroke.

Background and Purpose: Recent studies using automated perfusion imaging software have identified adults most likely to benefit from reperfusion therapies in extended time windows. The time course of penumbral tissue is poorly characterized in childhood arterial ischemic stroke (AIS). We explore the feasibility of using automated perfusion-diffusion imaging software to characterize penumbra in childhood AIS. Methods: An observational cohort study of children with acute unilateral AIS presenting to our institution. Diffusion-weighted imaging and dynamic susceptibility contrast perfusion magnetic resonance imaging performed within 72 hours of symptom onset were necessary for inclusion. Perfusion-diffusion mismatch was estimated using RAPID software. Ischemic core was defined as apparent diffusion coefficient <620×10−6 mm2/s and hypoperfusion as Tmax >6 seconds. Favorable mismatch profile was defined as core volume <70 mL, mismatch volume ≥15 mL, and a mismatch ratio ≥1.8. Results: Twenty-nine children (median 8 years old, interquartile range, 4.4­14.6) were included (26 unilateral middle cerebral artery and 3 unilateral cerebellar infarcts). Median Pediatric National Institutes of Health Stroke Scale was 4 (interquartile range, 3­11). Most cases had cryptogenic (n=11) or focal cerebral arteriopathy (n=9) causes. Median time-to-imaging =13.7 hours (interquartile range, 7.5­25.3). RAPID detected an ischemic core in 19 (66%) patients. In the remaining cases, the mean apparent diffusion coefficient values were mostly higher than the threshold as the majority of these presentations were delayed (median >21 hours) and infarct volumes were small (<3.5 mL). Overall, 3 children, imaged at 3.75, 11, and 23.5 hours had favorable mismatch profiles. Conclusions: This study demonstrates it is feasible to rapidly assess perfusion-diffusion mismatch in childhood AIS using automated software. Favorable mismatch profiles, using adult-based parameters, persisted beyond the standard 4.5 hours window for thrombolysis, suggesting potential therapeutic benefit of RAPID use. Further work is required to determine the utility of perfusion-based imaging to guide clinical decision making, whether adult thresholds require modification in childhood AIS, and to investigate the effect of time-delay and cause on mismatch characteristics.

Development of brain white matter and math computation ability in children born very preterm and full-term.

Children born very preterm (VPT; <32 weeks' gestation) have alterations in brain white matter and poorer math ability than full-term (FT) peers. Diffusion-weighted magnetic resonance imaging studies suggest a link between white matter microstructure and math in VPT and FT children, although longitudinal studies using advanced modelling are lacking. In a prospective longitudinal cohort of VPT and FT children we used Fixel-Based Analysis to investigate associations between maturation of white matter fibre density (FD), fibre-bundle cross-section (FC), and combined fibre density and cross-section (FDC) and math computation ability at 7 (n = 136 VPT; n = 32 FT) and 13 (n = 130 VPT; n = 44 FT) years, as well as between change in white matter and math computation ability from 7 to 13 years (n = 103 VPT; n = 21 FT). In both VPT and FT children, higher FD, FC and FDC in visual, sensorimotor and cortico-thalamic/thalamo-cortical white matter tracts were associated with better math computation ability at 7 and 13 years. Longitudinally, accelerated maturation of the posterior body of the corpus callosum (FDC) was associated with greater math computation development. White matter-math associations were similar for VPT and FT children. In conclusion, white matter maturation is associated with math computation ability across late childhood, irrespective of birth group.

Diffusion MRI tractography for neurosurgery: the basics, current state, technical reliability and challenges.

Diffusion magnetic resonance imaging (dMRI) tractography is currently the only imaging technique that allows for non-invasive delineation and visualisation of white matter (WM) tractsin vivo,prompting rapid advances in related fields of brain MRI research in recent years. One of its major clinical applications is for pre-surgical planning and intraoperative image guidance in neurosurgery, where knowledge about the location of WM tracts nearby the surgical target can be helpful to guide surgical resection and optimise post-surgical outcomes. Surgical injuries to these WM tracts can lead to permanent neurological and functional deficits, making the accuracy of tractography reconstructions paramount. The quality of dMRI tractography is influenced by many modifiable factors, ranging from MRI data acquisition through to the post-processing of tractography output, with the potential of error propagation based on decisions made at each and subsequent processing steps. Research over the last 25 years has significantly improved the anatomical accuracy of tractography. An updated review about tractography methodology in the context of neurosurgery is now timely given the thriving research activities in dMRI, to ensure more appropriate applications in the clinical neurosurgical realm. This article aims to review the dMRI physics, and tractography methodologies, highlighting recent advances to provide the key concepts of tractography-informed neurosurgery, with a focus on the general considerations, the current state of practice, technical challenges, potential advances, and future demands to this field.