Association of cerebral metabolic rate following therapeutic hypothermia with 18-month neurodevelopmental outcomes after neonatal hypoxic ischemic encephalopathy.

BACKGROUND: Therapeutic hypothermia (TH) is standard of care for moderate to severe neonatal hypoxic ischemic encephalopathy (HIE) but many survivors still suffer lifelong disabilities and benefits of TH for mild HIE are under active debate. Development of objective diagnostics, with sensitivity to mild HIE, are needed to select, guide, and assess response to treatment. The objective of this study was to determine if cerebral oxygen metabolism (CMRO2) in the days after TH is associated with 18-month neurodevelopmental outcomes as the first step in evaluating CMRO2's potential as a diagnostic for HIE. Secondary objectives were to compare associations with clinical exams and characterise the relationship between CMRO2 and temperature during TH. METHODS: This was a prospective, multicentre, observational, cohort study of neonates clinically diagnosed with HIE and treated with TH recruited from the tertiary neonatal intensive care units (NICUs) of Boston Children's Hospital, Brigham and Women's Hospital, and Beth Israel Deaconess Medical Center between December 2015 and October 2019 with follow-up to 18 months. In total, 329 neonates ≥34 weeks gestational age admitted with perinatal asphyxia and suspected HIE were identified. 179 were approached, 103 enrolled, 73 received TH, and 64 were included. CMRO2 was measured at the NICU bedside by frequency-domain near-infrared and diffuse correlation spectroscopies (FDNIRS-DCS) during the late phases of hypothermia (C), rewarming (RW) and after return to normothermia (NT). Additional variables were body temperature and clinical neonatal encephalopathy (NE) scores, as well as findings from magnetic resonance imaging (MRI) and spectroscopy (MRS). Primary outcome was the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) at 18 months, normed (SD) to 100 (15). FINDINGS: Data quality for 58 neonates was sufficient for analysis. CMRO2 changed by 14.4% per °C (95% CI, 14.2-14.6) relative to its baseline at NT while cerebral tissue oxygen extraction fraction (cFTOE) changed by only 2.2% per °C (95% CI, 2.1-2.4) for net changes from C to NT of 91% and 8%, respectively. Follow-up data for 2 were incomplete, 33 declined and 1 died, leaving 22 participants (mean [SD] postnatal age, 19.1 [1.2] month; 11 female) with mild to moderate HIE (median [IQR] NE score, 4 [3-6]) and 21 (95%) with BSID-III scores >85 at 18 months. CMRO2 at NT was positively associated with cognitive and motor composite scores (ß (SE) = 4.49 (1.55) and 2.77 (1.00) BSID-III points per 10-10 moL/dl × mm2/s, P = 0.009 and P = 0.01 respectively; linear regression); none of the other measures were associated with the neurodevelopmental outcomes. INTERPRETATION: Point of care measures of CMRO2 in the NICU during C and RW showed dramatic changes and potential to assess individual response to TH. CMRO2 following TH outperformed conventional clinical evaluations (NE score, cFTOE, and MRI/MRS) at predicting cognitive and motor outcomes at 18 months for mild to moderate HIE, providing a promising objective, physiologically-based diagnostic for HIE. FUNDING: This clinical study was funded by an NIH grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, United States (R01HD076258).

A Three-Dimensional (3D) Evaluation Unveiling if the Anterior Mandible Is Truly a Safe Zone for Implant Placement.

Background Dental implants are increasingly being used in the rehabilitation of the edentulous areas in the maxilla and mandible. The anterior mandible is considered a safe zone for implant placement, but clinicians often find it challenging to control bleeding in this area. This is due to the presence of the sublingual artery, which can be of varying dimensions and can cause severe bleeding. This can be of higher significance in patients with high or uncontrolled blood pressure and in patients on blood thinners like Aspirin or Coumadin where establishing a clot can be difficult. With newer guidelines recommending that medication be discontinued only a few hours before surgery and that bleeding be managed locally, this issue has become even more challenging. With three-dimensional (3D) imaging using cone beam computed tomography (CBCT) becoming more common for implant planning, the presence of the sublingual artery can be evaluated and incorporated into the treatment plan. The objective of this study is to evaluate the 3D location of the sublingual artery in the edentulous anterior mandible of CBCT scans of patients referred for dental implant therapy. Methodology A total of 50 de-identified CBCT scans with an edentulous anterior mandible referred for dental implant therapy were evaluated for this study. Cross-sectional images were generated using a CBCT reconstruction program INVIVO-5 (Anatomage, San Jose, CA, USA). After the sublingual artery was localized, measurement was conducted from a standardized point on the alveolar crest to the artery's entry point on the lingual aspect. Measurements were also obtained from the terminal point of the artery's course to the buccal cortical plate. Alveolar crest can either resorb or be subjected to alveoloplasty during implant placement, similar measurements were also done from a standardized point on the inferior cortical border of the mandible to the artery's entry points on the lingual aspect. Two oral and maxillofacial radiologists conducted all measurements. Results It was found that the median value of the sublingual artery from the alveolar crest to the level of entry (V1) was 6.78, the vertical measurement of the artery coursing into the alveolar bone was ~4.03 mm (V2), the vertical measurement of the artery's position within the alveolar bone at the terminal point form the crest was ~11.71 (V3), and the inferior vertical measurement from the course of the artery to the inferior border of the mandible was 9.60 mm. The artery extended about ~8.3 mm within the alveolar bone from the lingual cortex (H1), and the artery was located about 4.97 mm away from the buccal cortex (H2). Cronbach's Alpha test showed high interoperator reliability.  Conclusions In this retrospective study, the sublingual artery was noted to be at a critical location in the potential implant site. A site-specific evaluation using CBCT can help in localizing and avoiding perforation of the sublingual artery.

Cone Beam Computed Tomography (CBCT) Evaluation of Alveolar Bone Thickness and Root Angulation in Anterior Maxilla for Planning Immediate Implant Placement.

OBJECTIVE:  This retrospective study aimed to measure the labial, palatal, mesial, and distal bone thickness around maxillary central and lateral incisors and canines and height from crest to apex, using cone beam computed tomography (CBCT) images and compare the results based on gender. The second objective of the study was to measure root angulation on CBCT images and its relation with the labial cortical thicknesses.  Material and Methods: After the Institutional Review Board (IRB) approval, a total of 140 CBCT volumes were included in this study according to the set criteria. On each scan, right-side maxillary central, lateral incisors, and canine were selected for the measurements. All the measurements were done at three levels at the alveolar crest (L1), mid-root (L2), and apical region (L3) for each tooth.  Results: The Student's t-test was performed to compare the result of buccal, palatal, mesial, and distal bone thickness, angulation, and height of all subjects. Buccal alveolar bone thickness was minimum at the mid-root region, and the palatal bone thickness was minimum at the crestal region. The mesial bone thickness was minimum at the mid-root level, and distal bone thickness was minimum at the crest level. The available bone height was maximum at the lateral incisor and equal for the central incisor and canine. The canine was the most angulated tooth. CONCLUSION:  Cone beam computed tomography is a reliable imaging modality to evaluate pre-surgical immediate implant sites and measure alveolar bone thickness. The canine was the most angulated tooth with more buccal alveolar bone thickness.

Bilateral Stafne Bone Cavity in the Body of the Mandible: An Unusual Case Report and Literature Review.

Stafne defect also known as Stafne bone cavity is a lingual surface depression generally found in the posterior mandible. This entity is usually unilateral and asymptomatic, found during routine dental radiographic evaluation. Stafne defect appears as a well-defined, oval, corticated entity located below the inferior alveolar canal. These entities are the inclusion of the salivary gland tissues. In this case report, we present the case of a bilateral Stafne defect that was asymmetrically located in the mandible and was incidentally detected on the cone-beam computed tomography scan taken for implant treatment planning. This case report highlights the significance of three-dimensional imaging and correctly diagnosing the incidental findings within the scan.

Morphological Features of Language Regions in Individuals with Tuberous Sclerosis Complex.

A significant number of individuals with tuberous sclerosis complex (TSC) exhibit language difficulties. Here, we examined the language-related brain morphometry in 59 participants (7 participants with TSC and comorbid autism spectrum disorder (ASD) (TSC + ASD), 13 with TSC but no ASD (TSC-ASD), 10 with ASD-only (ASD), and 29 typically developing (TD) controls). A hemispheric asymmetry was noted in surface area and gray matter volume of several cortical language areas in TD, ASD, and TSC-ASD groups, but not in TSC + ASD group. TSC + ASD group demonstrated increased cortical thickness and curvature values in multiple language regions for both hemispheres, compared to other groups. After controlling for tuber load in the TSC groups, within-group differences stayed the same but the differences between TSC-ASD and TSC + ASD were no longer statistically significant. These preliminary findings suggest that comorbid ASD in TSC as well as tuber load in TSC is associated with changes in the morphometry of language regions. Future studies with larger sample sizes will be needed to confirm these findings.

Diffusion-Weighted Magnetic Resonance Imaging Demonstrates White Matter Alterations in Watershed Regions in Children With Moyamoya Without Stroke or Silent Infarct.

BACKGROUND: Moyamoya is a disease with progressive cerebral arterial stenosis leading to stroke and silent infarct. Diffusion-weighted magnetic resonance imaging (dMRI) studies show that adults with moyamoya have significantly lower fractional anisotropy (FA) and higher mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) compared with controls, which raises concern for unrecognized white matter injury. Children with moyamoya have significantly lower FA and higher MD in their white matter compared with controls. However, it is unknown which white matter tracts are affected in children with moyamoya. METHODS: We present a cohort of 15 children with moyamoya with 24 affected hemispheres without stroke or silent infarct compared with 25 controls. We analyzed dMRI data using unscented Kalman filter tractography and extracted major white matter pathways with a fiber clustering method. We compared the FA, MD, AD, and RD in each segmented white matter tract and combined white matter tracts found within the watershed region using analysis of variance. RESULTS: Age and sex were not significantly different between children with moyamoya and controls. Specific white matter tracts affected included inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, thalamofrontal, uncinate fasciculus, and arcuate fasciculus. Combined watershed region white matter tracts in children with moyamoya had significantly lower FA (-7.7% ± 3.2%, P = 0.02) and higher MD (4.8% ± 1.9%, P = 0.01) and RD (8.7% ± 2.8%, P = 0.002). CONCLUSIONS: Lower FA with higher MD and RD is concerning for unrecognized white matter injury. Affected tracts were located in watershed regions suggesting that the findings may be due to chronic hypoperfusion. These findings support the concern that children with moyamoya without overt stroke or silent infarction are sustaining ongoing injury to their white matter microstructure and provide practitioners with a noninvasive method of more accurately assessing disease burden in children with moyamoya.

Trifurcated Mental Foramina: A Cone-Beam Computed Tomography Incidental Finding During the Implant Treatment Planning.

The mental foramen is a known skull anatomical structure located bilaterally on the mandible along the buccal cortical plate. It is located approximately between the roots of premolars in the anteroposterior dimension, and its supero-inferior level on the alveolar height varies in every individual. The position of the mental foramen is very crucial when surgical interventions are planned in the area. An accessory mental foramina can be very well detected in the three-dimensional (3D) imaging modality, especially in 3D volume rendering images. It can still be appreciated in two-dimensional (2D) imaging modalities such as a panoramic; however, at times it can be confused with periapical pathology, especially in cases where caries are present in the teeth. Three-dimensional imaging modality plays a critical role in identifying such anatomical variation, and hence, it is important to evaluate any surgical site in three dimensions prior to surgical intervention.

Idiopathic lingual mandibular sequestration and its relationship to medication-related osteonecrosis of the jaws (MRONJ): mini review.

OBJECTIVE: Idiopathic lingual mandibular sequestration is an uncommon condition that affects the lingual aspect of the mandible and may result in a necrosis of the jaw that is clinically indistinguishable from medication-related osteonecrosis of the jaw. This condition, however, is not associated with the intake of antiresorptive medication and may not require the same safeguards for extended periods of time. The etiology of idiopathic lingual mandibular sequestration is still unknown although trauma has been shown to play an important role. METHOD AND MATERIALS: PubMed and the Cochrane Library were used to retrieve papers written in English through the years 1970 to 2021 using the key words "idiopathic osteonecrosis," "lingual sequestration," and "idiopathic jaw sequestration." In addition, clinical presentation of the lesion was included. RESULTS: Idiopathic lingual mandibular sequestration is a benign, mostly self-limiting condition distinct from medication- related osteonecrosis of the jaw. CONCLUSION: The dental clinician should be familiar with this condition and include it in their differential diagnosis when exposed bone is present with no history of radiation to the area or intake of antiresorptive medication. The course of the condition is usually very mild and may be self-limiting and usually does not require surgical intervention.

A Role for Data Science in Precision Nutrition and Early Brain Development.

Multimodal brain magnetic resonance imaging (MRI) can provide biomarkers of early influences on neurodevelopment such as nutrition, environmental and genetic factors. As the exposure to early influences can be separated from neurodevelopmental outcomes by many months or years, MRI markers can serve as an important intermediate outcome in multivariate analyses of neurodevelopmental determinants. Key to the success of such work are recent advances in data science as well as the growth of relevant data resources. Multimodal MRI assessment of neurodevelopment can be supplemented with other biomarkers of neurodevelopment such as electroencephalograms, magnetoencephalogram, and non-imaging biomarkers. This review focuses on how maternal nutrition impacts infant brain development, with three purposes: (1) to summarize the current knowledge about how nutrition in stages of pregnancy and breastfeeding impact infant brain development; (2) to discuss multimodal MRI and other measures of early neurodevelopment; and (3) to discuss potential opportunities for data science and artificial intelligence to advance precision nutrition. We hope this review can facilitate the collaborative march toward precision nutrition during pregnancy and the first year of life.

Increased Breastfeeding Proportion Is Associated with Improved Gross Motor Skills at 3-5 Years of Age: A Pilot Study.

Breastmilk provides key nutrients and bio-active factors that contribute to infant neurodevelopment. Optimizing maternal nutrition could provide further benefit to psychomotor outcomes. Our observational cohort pilot study aims to determine if breastfeeding extent and breastmilk nutrients correlate with psychomotor outcomes at school age. The breastfeeding proportion at 3 months of age and neurodevelopmental outcomes at 3-5 years of age were recorded for 33 typically developing newborns born after uncomplicated pregnancies. The association between categorical breastfeeding proportion and neurodevelopmental outcome scores was determined for the cohort using a Spearman correlation with and without the inclusion of parental factors. Vitamin E and carotenoid levels were determined in breastmilk samples from 14 of the mothers. After the inclusion of parental education and income as covariates, motor skill scores positively correlated with breastmilk contents of α-tocopherol (Spearman coefficient 0.88, p-value = 0.02), translutein (0.98, p-value = 0.0007), total lutein (0.92, p-value = 0.01), and zeaxanthin (0.93, p-value = 0.0068). Problem solving skills negatively correlated with the levels of the RSR enantiomer of α-tocopherol (-0.86, p-value = 0.03). Overall, higher exposure to breastfeeding was associated with improved gross motor and problem-solving skills at 3-5 years of age. The potential of α-tocopherol, lutein, and zeaxanthin intake to provide neurodevelopmental benefit is worthy of further investigation.

Improving Infant Hydrocephalus Outcomes in Uganda: A Longitudinal Prospective Study Protocol for Predicting Developmental Outcomes and Identifying Patients at Risk for Early Treatment Failure after ETV/CPC.

Infant hydrocephalus poses a severe global health burden; 80% of cases occur in the developing world where patients have limited access to neurosurgical care. Surgical treatment combining endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC), first practiced at CURE Children's Hospital of Uganda (CCHU), is as effective as standard ventriculoperitoneal shunt (VPS) placement while requiring fewer resources and less post-operative care. Although treatment focuses on controlling ventricle size, this has little association with treatment failure or long-term outcome. This study aims to monitor the progression of hydrocephalus and treatment response, and investigate the association between cerebral physiology, brain growth, and neurodevelopmental outcomes following surgery. We will enroll 300 infants admitted to CCHU for treatment. All patients will receive pre/post-operative measurements of cerebral tissue oxygenation (SO2), cerebral blood flow (CBF), and cerebral metabolic rate of oxygen consumption (CMRO2) using frequency-domain near-infrared combined with diffuse correlation spectroscopies (FDNIRS-DCS). Infants will also receive brain imaging, to monitor tissue/ventricle volume, and neurodevelopmental assessments until two years of age. This study will provide a foundation for implementing cerebral physiological monitoring to establish evidence-based guidelines for hydrocephalus treatment. This paper outlines the protocol, clinical workflow, data management, and analysis plan of this international, multi-center trial.

Quantification of magnetic resonance spectroscopy data using a combined reference: Application in typically developing infants.

Quantification of proton magnetic resonance spectroscopy (1 H-MRS) data is commonly performed by referencing the ratio of the signal from one metabolite, or metabolite group, to that of another, or to the water signal. Both approaches have drawbacks: ratios of two metabolites can be difficult to interpret because study effects may be driven by either metabolite, and water-referenced data must be corrected for partial volume and relaxation effects in the water signal. Here, we introduce combined reference (CRef) analysis, which compensates for both limitations. In this approach, metabolites are referenced to the combined signal of several reference metabolites or metabolite groups. The approach does not require the corrections necessary for water scaling and produces results that are less sensitive to the variation of any single reference signal, thereby aiding the interpretation of results. We demonstrate CRef analysis using 202 1 H-MRS acquisitions from the brains of 140 infants, scanned at approximately 1 and 3 months of age. We show that the combined signal of seven reference metabolites or metabolite groups is highly correlated with the water signal, corrected for partial volume and relaxation effects associated with cerebral spinal fluid. We also show that the combined reference signal is equally or more uniform across subjects than the reference signals from single metabolites or metabolite groups. We use CRef analysis to quantify metabolite concentration changes during the first several months of life in typically developing infants.

Assessment of Maternal Macular Pigment Optical Density (MPOD) as a Potential Marker for Dietary Carotenoid Intake during Lactation in Humans.

Pregnancy and lactation can change the maternal nutrient reserve. Non-invasive, quantitative markers of maternal nutrient intake could enable personalized dietary recommendations that improve health outcomes in mothers and infants. Macular pigment optical density (MPOD) is a candidate marker, as MPOD values generally reflect carotenoid intake. We evaluated the association of MPOD with dietary and breastmilk carotenoids in postpartum women. MPOD measurements and dietary intake of five carotenoids were obtained from 80 mothers in the first three months postpartum. Breastmilk samples from a subset of mothers were analyzed to determine their nutrient composition. The association between MPOD and dietary or breastmilk carotenoids was quantitatively assessed to better understand the availability and mobilization of carotenoids. Our results showed that dietary α-carotene was positively correlated with MPOD. Of the breastmilk carotenoids, 13-cis-lutein and trans-lutein were correlated with MPOD when controlled for the total lutein in breastmilk. Other carotenoids in breastmilk were not associated with MPOD. Maternal MPOD is positively correlated with dietary intake of α-carotene in the early postpartum period, as well as with the breastmilk content of lutein. MPOD may serve as a potential marker for the intake of carotenoids, especially α-carotene, in mothers in the early postpartum period.

Brain Characteristics Noted Prior to and Following Cranial Orthotic Treatment.

OBJECTIVE: This case report aims to assess a potential association between cranial asymmetry, brain deformation, and associated developmental delay. STUDY DESIGN: Two infants born at ≥37 weeks pursuing cranial orthotic treatment for severe Deformational Plagiocephaly (DP) (cranial vault asymmetry index >8.75%) underwent developmental assessment using Mullen Scales of Early Learning (MSEL) and non-sedated brain structural and diffusion magnetic resonance imaging (MRI) prior to and following cranial orthotic treatment. RESULTS: In both infants with DP, tractography results revealed alterations in the white matter pathways of the brain. Both infants also had low to low/normal visual receptivity and fine motor skills. After cranial orthotic treatment, cranial asymmetry improved but did not completely resolve, tractography demonstrated a change toward normalized white matter pathways, and visual receptivity and fine motor skills improved. CONCLUSIONS: These preliminary findings suggest a potential link between DP, altered brain structures, and developmental assessment. Further investigation with a larger sample is warranted.

Maternal Dietary Intake of Omega-3 Fatty Acids Correlates Positively with Regional Brain Volumes in 1-Month-Old Term Infants.

Maternal nutrition is an important factor for infant neurodevelopment. However, prior magnetic resonance imaging (MRI) studies on maternal nutrients and infant brain have focused mostly on preterm infants or on few specific nutrients and few specific brain regions. We present a first study in term-born infants, comprehensively correlating 73 maternal nutrients with infant brain morphometry at the regional (61 regions) and voxel (over 300 000 voxel) levels. Both maternal nutrition intake diaries and infant MRI were collected at 1 month of life (0.9 ± 0.5 months) for 92 term-born infants (among them, 54 infants were purely breastfed and 19 were breastfed most of the time). Intake of nutrients was assessed via standardized food frequency questionnaire. No nutrient was significantly correlated with any of the volumes of the 61 autosegmented brain regions. However, increased volumes within subregions of the frontal cortex and corpus callosum at the voxel level were positively correlated with maternal intake of omega-3 fatty acids, retinol (vitamin A) and vitamin B12, both with and without correction for postmenstrual age and sex (P < 0.05, q < 0.05 after false discovery rate correction). Omega-3 fatty acids remained significantly correlated with infant brain volumes after subsetting to the 54 infants who were exclusively breastfed, but retinol and vitamin B12 did not. This provides an impetus for future larger studies to better characterize the effect size of dietary variation and correlation with neurodevelopmental outcomes, which can lead to improved nutritional guidance during pregnancy and lactation.

Abnormalities in cerebral hemodynamics and changes with surgical intervention in neonates with congenital heart disease.

OBJECTIVE: To use novel optical techniques to measure perioperative cerebral hemodynamics of diverse congenital heart disease (CHD) groups (two-ventricle, d-transposition of the great arteries [TGA], and single ventricle [SV]) and (1) compare CHD groups with healthy controls preoperatively and (2) compare preoperative and postoperative values within each CHD group. METHODS: Frequency-domain near-infrared spectroscopy and diffuse correlation spectroscopy were used to measure cerebral oxygen saturation, cerebral blood volume, cerebral blood flow index, cerebral oxygen extraction fraction (OEF, calculated using arterial oxygen saturation and cerebral oxygen saturation), and an index of cerebral metabolic rate of oxygen consumption in control and CHD neonates. Preoperative CHD measures were compared with controls. Preoperative and postoperative measures were compared within each CHD group. RESULTS: In total, 31 CHD neonates (7 two-ventricle, 11 TGA, 13 SV) and 13 controls were included. Only neonates with SV CHD displayed significantly lower preoperative cerebral blood flow index (P < .04) than controls. TGA and SV groups displayed greater OEF (P < .05) during the preoperative period compared with controls. Compared with the preoperative state, postoperative neonates with TGA had a greater arterial oxygen saturation with lower OEF. CONCLUSIONS: Differences in cerebral hemodynamics and oxygen metabolism were observed in diverse CHD groups compared with controls. Increased OEF appears to be a compensatory mechanism in neonates with TGA and SV. Studies are needed to understand the relationship of these metrics to outcome and their potential to guide interventions to improve outcome.

Non-invasive Assessment of Cerebral Blood Flow and Oxygen Metabolism in Neonates during Hypothermic Cardiopulmonary Bypass: Feasibility and Clinical Implications.

The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time. This pilot study aims to evaluate cerebral blood flow (CBF) and oxygen metabolism (CMRO2) intraoperatively in neonates by combining two novel non-invasive optical techniques: frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS). CBF and CMRO2 were quantified before, during and after deep hypothermic cardiopulmonary bypass (CPB) in nine neonates. Our results show significantly decreased CBF and CMRO2 during hypothermic CPB. More interestingly, a change of coupling between both variables is observed during deep hypothermic CPB in all subjects. Our results are consistent with previous studies using invasive techniques, supporting the concept of FD-NIRS/DCS as a promising technology to monitor cerebral physiology in neonates providing the potential for individual optimization of surgical management.

Perioperative cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle physiology.

Congenital heart disease (CHD) patients are at risk for neurodevelopmental delay. The etiology of these delays is unclear, but abnormal prenatal cerebral maturation and postoperative hemodynamic instability likely play a role. A better understanding of these factors is needed to improve neurodevelopmental outcome. In this study, we used bedside frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) to assess cerebral hemodynamics and oxygen metabolism in neonates with single-ventricle (SV) CHD undergoing surgery and compared them to controls. Our goals were 1) to compare cerebral hemodynamics between unanesthetized SV and healthy neonates, and 2) to determine if FDNIRS-DCS could detect alterations in cerebral hemodynamics beyond cerebral hemoglobin oxygen saturation (SO 2). Eleven SV neonates were recruited and compared to 13 controls. Preoperatively, SV patients showed decreased cerebral blood flow (CBFi ), cerebral oxygen metabolism (CMRO 2i ) and SO 2; and increased oxygen extraction fraction (OEF) compared to controls. Compared to preoperative values, unstable postoperative SV patients had decreased CMRO 2i and CBFi , which returned to baseline when stable. However, SO 2 showed no difference between unstable and stable states. Preoperative SV neonates are flow-limited and show signs of impaired cerebral development compared to controls. FDNIRS-DCS shows potential to improve assessment of cerebral development and postoperative hemodynamics compared to SO 2 alone.