Quantitative noninvasive measurement of cerebrospinal fluid flow in shunted hydrocephalus.

OBJECTIVE: Standard MRI protocols lack a quantitative sequence that can be used to evaluate shunt-treated patients with a history of hydrocephalus. The objective of this study was to investigate the use of phase-contrast MRI (PC-MRI), a quantitative MR sequence, to measure CSF flow through the shunt and demonstrate PC-MRI as a useful adjunct in the clinical monitoring of shunt-treated patients. METHODS: The rapid (96 seconds) PC-MRI sequence was calibrated using a flow phantom with known flow rates ranging from 0 to 24 mL/hr. Following phantom calibration, 21 patients were scanned with the PC-MRI sequence. Multiple, successive proximal and distal measurements were gathered in 5 patients to test for measurement error in different portions of the shunt system and to determine intrapatient CSF flow variability. The study also includes the first in vivo validations of PC-MRI for CSF shunt flow by comparing phase-contrast-measured flow rate with CSF accumulation in a collection burette obtained in patients with externalized distal shunts. RESULTS: The PC-MRI sequence successfully measured CSF flow rates ranging from 6 to 54 mL/hr in 21 consecutive pediatric patients. Comparison of PC-MRI flow measurement and CSF volume collected in a bedside burette showed good agreement in a patient with an externalized distal shunt. Notably, the distal portion of the shunt demonstrated lower measurement error when compared with PC-MRI measurements acquired in the proximal catheter. CONCLUSIONS: The PC-MRI sequence provided accurate and reliable clinical measurements of CSF flow in shunt-treated patients. This work provides the necessary framework to include PC-MRI as an immediate addition to the clinical setting in the noninvasive evaluation of shunt function and in future clinical investigations of CSF physiology.

A Scoping Review of the Mechanisms Underlying Developmental Anesthetic Neurotoxicity.

Although anesthesia makes painful or uncomfortable diagnostic and interventional health care procedures tolerable, it may also disrupt key cellular processes in neurons and glia, harm the developing brain, and thereby impair cognition and behavior in children. Many years of studies using in vitro, animal behavioral, retrospective database studies in humans, and several prospective clinical trials in humans have been invaluable in discerning the potential toxicity of anesthetics. The objective of this scoping review was to synthetize the evidence from preclinical studies for various mechanisms of toxicity across diverse experimental designs and relate their findings to those of recent clinical trials in real-world settings.

Cerebrovascular responses to a 90° tilt in healthy neonates.

BACKGROUND: Tilts can induce alterations in cerebral hemodynamics in healthy neonates, but prior studies have only examined systemic parameters or used small tilt angles (<90°). The healthy neonatal population, however, are commonly subjected to large tilt angles (≥90°). We sought to characterize the cerebrovascular response to a 90° tilt in healthy term neonates. METHODS: We performed a secondary descriptive analysis on 44 healthy term neonates. We measured cerebral oxygen saturation (rcSO2), oxygen saturation (SpO2), heart rate (HR), breathing rate (BR), and cerebral fractional tissue oxygen extraction (cFTOE) over three consecutive 90° tilts. These parameters were measured for 2-min while neonates were in a supine (0°) position and 2-min while tilted to a sitting (90°) position. We measured oscillometric mean blood pressure (MBP) at the start of each tilt. RESULTS: rcSO2 and BR decreased significantly in the sitting position, whereas cFTOE, SpO2, and MBP increased significantly in the sitting position. We detected a significant position-by-time interaction for all physiological parameters. CONCLUSION: A 90° tilt induces a decline in rcSO2 and an increase in cFTOE in healthy term neonates. Understanding the normal cerebrovascular response to a 90° tilt in healthy neonates will help clinicians to recognize abnormal responses in high-risk infant populations. IMPACT: Healthy term neonates (≤14 days old) had decreased cerebral oxygen saturation (~1.1%) and increased cerebral oxygen extraction (~0.01) following a 90° tilt. We detected a significant position-by-time interaction with all physiological parameters measured, suggesting the effect of position varied across consecutive tilts. No prior study has characterized the cerebral oxygen saturation response to a 90° tilt in healthy term neonates.

Improved cerebrovascular reactivity mapping using coherence weighted general linear model in the frequency domain.

Cerebrovascular reactivity (CVR) is a prognostic indicator of cerebrovascular health. Estimating CVR from endogenous end-tidal carbon dioxide (CO2) fluctuation and MRI signal recorded under resting state can be difficult due to the poor signal-to-noise ratio (SNR) of signals. Thus, we aimed to improve the method of estimating CVR from end-tidal CO2 and MRI signals. We proposed a coherence weighted general linear model (CW-GLM) to estimate CVR from the Fourier coefficients weighted by the signal coherence in frequency domain, which confers two advantages. First, it requires no signal alignment in time domain, which simplifies experimental methods. Second, it limits the GLM analysis within the frequency band where CO2 and MRI signals are highly correlated, which automatically suppresses noise and nuisance signals. We compared the performance of our method with time-domain GLM (TD-GLM) and frequency-domain GLM (FD-GLM) in both synthetic and in-vivo data; wherein we calculated CVR from signals recorded under both resting state and sinusoidal stimulus. In synthetic data, CW-GLM has a remarkable performance on CVR estimation from narrow band signals with a mean-absolute error of 0.7 % (gray matter) and 1.2 % (white matter), which was lower than all the other methods. Meanwhile, CW-GLM maintains a comparable performance on CVR estimation from resting signals, with a mean-absolute error of 4.1 % (gray matter) and 8 % (white matter). The superior performance was maintained across the 36 in-vivo measurements, with CW-GLM exhibiting limits of agreement of -16.7 % - 9.5 % between CVR calculated from the resting and sinusoidal CO2 paradigms which was 12 % - 209 % better than current time-domain methods. Evaluating of the cross-coherence spectrum revealed highest signal coherence within the frequency band from 0.01 Hz to 0.05 Hz, which overlaps with previously recommended frequency band (0.02 Hz to 0.04 Hz) for CVR analysis. Our data demonstrates that CW-GLM can work as a self-adaptive band-pass filter to improve CVR robustness, while also avoiding the need for signal temporal alignment.

Brain BOLD and NIRS response to hyperoxic challenge in sickle cell disease and chronic anemias.

PURPOSE: Congenital anemias, including sickle cell anemia and thalassemia, are associated with cerebral tissue hypoxia and heightened stroke risks. Recent works in sickle cell disease mouse models have suggested that hyperoxia respiratory challenges can identify regions of the brain having chronic tissue hypoxia. Therefore, this work investigated differences in hyperoxic response and regional cerebral oxygenation between anemic and healthy subjects. METHODS: A cohort of 38 sickle cell disease subjects (age 22 ± 8 years, female 39%), 25 non-sickle anemic subjects (age 25 ± 11 years, female 52%), and 31 healthy controls (age 25 ± 10 years, female 68%) were examined. A hyperoxic gas challenge was performed with concurrent acquisition of blood oxygen level-dependent (BOLD) MRI and near-infrared spectroscopy (NIRS). In addition to hyperoxia-induced changes in BOLD and NIRS, global measurements of cerebral blood flow, oxygen delivery, and cerebral metabolic rate of oxygen were obtained and compared between the three groups. RESULTS: Regional BOLD changes were not able to identify brain regions of flow limitation in chronically anemic patients. Higher blood oxygen content and tissue oxygenation were observed during hyperoxia gas challenge. Both control and anemic groups demonstrated lower blood flow, oxygen delivery, and metabolic rate compared to baseline, but the oxygen metabolism in anemic subjects were abnormally low during hyperoxic exposure. CONCLUSION: These results indicated that hyperoxic respiratory challenge could not be used to identify chronically ischemic brain. Furthermore, the low hyperoxia-induced metabolic rate suggested potential negative effects of prolonged oxygen therapy and required further studies to evaluate the risk for hyperoxia-induced oxygen toxicity and cerebral dysfunction.

Imputation models and error analysis for phase contrast MR cerebral blood flow measurements.

Cerebral blood flow (CBF) supports brain metabolism. Diseases impair CBF, and pharmacological agents modulate CBF. Many techniques measure CBF, but phase contrast (PC) MR imaging through the four arteries supplying the brain is rapid and robust. However, technician error, patient motion, or tortuous vessels degrade quality of the measurements of the internal carotid (ICA) or vertebral (VA) arteries. We hypothesized that total CBF could be imputed from measurements in subsets of these 4 feeding vessels without excessive penalties in accuracy. We analyzed PC MR imaging from 129 patients, artificially excluded 1 or more vessels to simulate degraded imaging quality, and developed models of imputation for the missing data. Our models performed well when at least one ICA was measured, and resulted in R 2 values of 0.998-0.990, normalized root mean squared error values of 0.044-0.105, and intra-class correlation coefficient of 0.982-0.935. Thus, these models were comparable or superior to the test-retest variability in CBF measured by PC MR imaging. Our imputation models allow retrospective correction for corrupted blood vessel measurements when measuring CBF and guide prospective CBF acquisitions.

Development of an ultrafast brain MR neuronavigation protocol for ventricular shunt placement.

OBJECTIVE: Advancements in MRI technology have provided improved ways to acquire imaging data and to more seamlessly incorporate MRI into modern pediatric surgical practice. One such situation is image-guided navigation for pediatric neurosurgical procedures, including intracranial catheter placement. Image-guided surgery (IGS) requires acquisition of CT or MR images, but the former carries the risk of ionizing radiation and the latter is associated with long scan times and often requires pediatric patients to be sedated. The objective of this project was to circumvent the use of CT and standard-sequence MRI in ventricular neuronavigation by investigating the use of fast MR sequences on the basis of 3 criteria: scan duration comparable to that of CT acquisition, visualization of ventricular morphology, and image registration with surface renderings comparable to standard of care. The aim of this work was to report image development, implementation, and results of registration accuracy testing in healthy subjects. METHODS: The authors formulated 11 candidate MR sequences on the basis of the standard IGS protocol, and various scan parameters were modified, such as k-space readout direction, partial k-space acquisition, sparse sampling of k-space (i.e., compressed sensing), in-plane spatial resolution, and slice thickness. To evaluate registration accuracy, the authors calculated target registration error (TRE). A candidate sequence was selected for further evaluation in 10 healthy subjects. RESULTS: The authors identified a candidate imaging protocol, termed presurgical imaging with compressed sensing for time optimization (PICO). Acquisition of the PICO protocol takes 25 seconds. The authors demonstrated noninferior TRE for PICO (3.00 ± 0.19 mm) in comparison with the default MRI neuronavigation protocol (3.35 ± 0.20 mm, p = 0.20). CONCLUSIONS: The developed and tested sequence of this work allowed accurate intraoperative image registration and provided sufficient parenchymal contrast for visualization of ventricular anatomy. Further investigations will evaluate use of the PICO protocol as a substitute for CT and conventional MRI protocols in ventricular neuronavigation.

Quantitative Susceptibility Mapping: Translating an Investigative Research Tool into High Volume Clinical Diagnostic Imaging.

Quantitative susceptibility mapping (QSM) is an MRI-based technique for iron quantification of targeted tissue. QSM provides information relevant to clinicians in a broad range of diagnostic contexts, including sickle cell disease, inflammatory/demyelinating processes, and neoplasms. However, major MRI vendors do not offer QSM post-processing in a form ready for general use. This work describes a vendor-agnostic approach for scaling QSM analysis from a research technique to a routine diagnostic test. We provide the details needed to seamlessly integrate hardware, software, and clinical systems to provide QSM processing for a busy clinical radiology workflow. This approach can be generalized to other advanced MRI acquisitions and analyses with proven diagnostic utility, yet without crucial MR vendor support.

Pathophysiological Mechanisms Underlying Idiopathic Normal Pressure Hydrocephalus: A Review of Recent Insights.

The pathophysiologic mechanisms underpinning idiopathic normal pressure hydrocephalus (iNPH), a clinically diagnosed dementia-causing disorder, continue to be explored. An increasing body of evidence implicates multiple systems in the pathogenesis of this condition, though a unifying causative etiology remains elusive. Increased knowledge of the aberrations involved has shed light on the iNPH phenotype and has helped to guide prognostication for treatment with cerebrospinal fluid diversion. In this review, we highlight the central role of the cerebrovasculature in pathogenesis, from hydrocephalus formation to cerebral blood flow derangements, blood-brain barrier breakdown, and glymphatic pathway dysfunction. We offer potential avenues for increasing our understanding of how this disease occurs.

Algorithms for segmenting cerebral time-of-flight magnetic resonance angiograms from volunteers and anemic patients.

Purpose: To evaluate six cerebral arterial segmentation algorithms in a set of patients with a wide range of hemodynamic characteristics to determine real-world performance. Approach: Time-of-flight magnetic resonance angiograms were acquired from 33 subjects: normal controls ( N = 11 ), sickle cell disease ( N = 11 ), and non-sickle anemia ( N = 11 ) using a 3 Tesla Philips Achieva scanner. Six segmentation algorithms were tested: (1) Otsu's method, (2) K-means, (3) region growing, (4) active contours, (5) minimum cost path, and (6) U-net machine learning. Segmentation algorithms were tested with two region-selection methods: global, which selects the entire volume; and local, which iteratively tracks the arteries. Five slices were manually segmented from each patient by two readers. Agreement between manual and automatic segmentation was measured using Matthew's correlation coefficient (MCC). Results: Median algorithm segmentation times ranged from 0.1 to 172.9 s for a single angiogram versus 10 h for manual segmentation. Algorithms had inferior performance to inter-observer vessel-based ( p < 0.0001 , MCC = 0.65 ) and voxel-based ( p < 0.0001 , MCC = 0.73 ) measurements. There were significant differences between algorithms ( p < 0.0001 ) and between patients ( p < 0.0042 ). Post-hoc analyses indicated (1) local minimum cost path performed best with vessel-based ( p = 0.0261 , MCC = 0.50 ) and voxel-based ( p = 0.0131 , MCC = 0.66 ) analyses; and (2) higher vessel-based performance in non-sickle anemia ( p = 0.0002 ) and lower voxel-based performance in sickle cell ( p = 0.0422 ) compared with normal controls. All reported MCCs are medians. Conclusions: The best-performing algorithm (local minimum cost path, voxel-based) had 9.59% worse performance than inter-observer agreement but was 3 orders of magnitude faster. Automatic segmentation was non-inferior in patients with sickle cell disease and superior in non-sickle anemia.

Individual red blood cell nitric oxide production in sickle cell anemia: Nitric oxide production is increased and sickle shaped cells have unique morphologic change compared to discoid cells.

Sickle cell anemia (SCA) is characterized by decreased red blood cell (RBC) deformability due to polymerization of deoxygenated hemoglobin, leading to abnormal mechanical properties of RBC, increased cellular adhesion, and microcirculatory obstruction. Prior work has demonstrated that NO• influences RBC hydration and deformability and is produced at a basal rate that increases under shear stress in normal RBC. Nevertheless, the origin and physiological relevance of nitric oxide (NO•) production and scavenging in RBC remains unclear. We aimed to assess the basal and shear-mediated production of NO• in RBC from SCA patients and control (CTRL) subjects. RBCs loaded with a fluorescent NO• detector, DAF-FM (4-Amino-5-methylamino- 2',7'-difluorofluorescein diacetate), were imaged in microflow channels over 30-min without shear stress, followed by a 30-min period under 0.5Pa shear stress. We utilized non-specific nitric oxide synthase (NOS) blockade and carbon monoxide (CO) saturation of hemoglobin to assess the contribution of NOS and hemoglobin, respectively, to NO• production. Quantification of DAF-FM fluorescence intensity in individual RBC showed an increase in NO• in SCA RBC at the start of the basal period; however, both SCA and CTRL RBC increased NO• by a similar quantity under shear. A subpopulation of sickle-shaped RBC exhibited lower basal NO• production compared to discoid RBC from SCA group, and under shear became more circular in the direction of shear when compared to discoid RBC from SCA and CTRL, which elongated. Both CO and NOS inhibition caused a decrease in basal NO• production. Shear-mediated NO• production was decreased by CO in all RBC, but was decreased by NOS blockade only in SCA. In conclusion, total NO• production is increased and shear-mediated NO• production is preserved in SCA RBC in a NOS-dependent manner. Sickle shaped RBC with inclusions have higher NO• production and they become more circular rather than elongated with shear.

Cerebral oxygen saturation and cerebrovascular instability in newborn infants with congenital heart disease compared to healthy controls.

OBJECTIVE: Infants with Congenital Heart Disease (CHD) are at risk for developmental delays, though the mechanisms of brain injury that impair development are unknown. Potential causes could include cerebral hypoxia and cerebrovascular instability. We hypothesized that we would detect significantly reduced cerebral oxygen saturation and greater cerebrovascular instability in CHD infants compared to the healthy controls. METHODS: We performed a secondary analysis on a sample of 43 term infants (28 CHD, 15 healthy controls) that assessed prospectively in temporal cross-section before or at 12 days of age. CHD infants were assessed prior to open-heart surgery. Cerebral oxygen saturation levels were estimated using Near-Infrared Spectroscopy, and cerebrovascular stability was assessed with the response of cerebral oxygen saturation after a postural change (supine to sitting). RESULTS: Cerebral oxygen saturation was 9 points lower in CHD than control infants in both postures (ß = -9.3; 95%CI = -17.68, -1.00; p = 0.028), even after controlling for differences in peripheral oxygen saturation. Cerebrovascular stability was significantly impaired in CHD compared to healthy infants (ß = -2.4; 95%CI = -4.12, -.61; p = 0.008), and in CHD infants with single ventricle compared with biventricular defects (ß = -1.5; 95%CI = -2.95, -0.05; p = 0.04). CONCLUSION: CHD infants had cerebral hypoxia and decreased cerebral oxygen saturation values following a postural change, suggesting cerebrovascular instability. Future longitudinal studies should assess the associations of cerebral hypoxia and cerebrovascular instability with long-term neurodevelopmental outcomes in CHD infants.

Reduced global cerebral oxygen metabolic rate in sickle cell disease and chronic anemias.

Anemia is the most common blood disorder in the world. In patients with chronic anemia, such as sickle cell disease or major thalassemia, cerebral blood flow increases to compensate for decreased oxygen content. However, the effects of chronic anemia on oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2 ) are less well understood. In this study, we examined 47 sickle-cell anemia subjects (age 21.7 ± 7.1, female 45%), 27 non-sickle anemic subjects (age 25.0 ± 10.4, female 52%) and 44 healthy controls (age 26.4 ± 10.6, female 71%) using MRI metrics of brain oxygenation and flow. Phase contrast MRI was used to measure resting cerebral blood flow, while T2 -relaxation-under-spin-tagging (TRUST) MRI with disease appropriate calibrations were used to measure OEF and CMRO2 . We observed that patients with sickle cell disease and other chronic anemias have decreased OEF and CMRO2 (respectively 27.4 ± 4.1% and 3.39 ± 0.71 ml O2 /100 g/min in sickle cell disease, 30.8 ± 5.2% and 3.53 ± 0.64 ml O2 /100 g/min in other anemias) compared to controls (36.7 ± 6.0% and 4.00 ± 0.65 ml O2 /100 g/min). Impaired CMRO2 was proportional to the degree of anemia severity. We further demonstrate striking concordance of the present work with pooled historical data from patients having broad etiologies for their anemia. The reduced cerebral oxygen extraction and metabolism are consistent with emerging data demonstrating increased non-nutritive flow, or physiological shunting, in sickle cell disease patients.

Calibration of T2 oximetry MRI for subjects with sickle cell disease.

PURPOSE: Cerebral T2 oximetry is a non-invasive imaging method to measure blood T2 and cerebral venous oxygenation. Measured T2 values are converted to oximetry estimates using carefully validated and potentially disease-specific calibrations. In sickle cell disease, red blood cells have abnormal cell shape and membrane properties that alter T2 oximetry calibration relationships in clinically meaningful ways. Previous in vitro works by two independent groups established potentially competing calibration models. METHODS: This study analyzed pooled datasets from these two studies to establish a unified and more robust sickle-specific calibration to serve as a reference standard in the field. RESULTS: Even though the combined calibration did not demonstrate statistical superiority compared to previous models, the calibration was unbiased compared to blood-gas co-oximetry and yielded limits of agreement of (-10.1%, 11.6%) in non-transfused subjects with sickle cell disease. In transfused patients, this study proposed a simple correction method based on individual hemoglobin S percentage that demonstrated reduced bias in saturation measurement compared to previous uncorrected sickle calibrations. CONCLUSION: The combined calibration is based on a larger range of hematocrit, providing greater confidence in the hematocrit-dependent model parameters, and yielded unbiased estimates to blood-gas co-oximetry measurements from both sites. Additionally, this work also demonstrated the need to correct for transfusion in T2 oximetry measurements for hyper-transfused sickle cell disease patients and proposes a correction method based on patient-specific hemoglobin S concentration.

MRI Automated T1 Signal Intensity Detection of Diffuse Brain Manganese Accumulation in Cirrhosis.

BACKGROUND AND PURPOSE: Cirrhosis is associated with diffuse brain manganese deposition, which results in increased signal intensity (SI) in the brain on T1-weighted images, most often visualized in the globus pallidus. The purpose of this study was to determine if automated image intensity measurements can detect SI differences in the basal ganglia and other regions reported to have manganese deposition in patients with cirrhosis compared with controls. METHODS: T1 FSPGR images were acquired on 28 patients with cirrhosis and 28 age-sex-matched controls. FreeSurfer T1 SI values were obtained for the globus pallidus, putamen, cerebral white matter, cerebral cortex, and brainstem. SI ratios were computed for globus pallidus normalized to white matter and brainstem. SI values and SI ratios were compared between groups using t-tests. RESULTS: Among people with cirrhosis, T1 SI was significantly increased in the globus pallidus, putamen, cerebral white matter, cerebral cortex, and brainstem (P< .001), and the globus pallidus to brainstem ratio was significantly increased (P< .001). No significant difference was seen for globus pallidus to cerebral white matter T1 SI ratio (P = .38). CONCLUSIONS: Automatic assessment of T1 SI allows for rapid, objective identification of widespread T1 shortening associated with manganese deposition in cirrhosis, consistent with the global deposition of neurotoxic manganese seen in pathology studies. This automated T1 assessment may have broader utility for other conditions beyond cirrhosis impacting T1 SI.

Quantitative perfusion mapping with induced transient hypoxia using BOLD MRI.

PURPOSE: Gadolinium-based dynamic susceptibility contrast (DSC) is commonly used to characterize blood flow in patients with stroke and brain tumors. Unfortunately, gadolinium contrast administration has been associated with adverse reactions and long-term accumulation in tissues. In this work, we propose an alternative deoxygenation-based DSC (dDSC) method that uses a transient hypoxia gas paradigm to deliver a bolus of paramagnetic deoxygenated hemoglobin to the cerebral vasculature for perfusion imaging. METHODS: Through traditional DSC tracer kinetic modeling, the MR signal change induced by this hypoxic bolus can be used to generate regional perfusion maps of cerebral blood flow, cerebral blood volume, and mean transit time. This gas paradigm and blood-oxygen-level-dependent (BOLD)-MRI were performed concurrently on a cohort of 66 healthy and chronically anemic subjects (age 23.5 ± 9.7, female 64%). RESULTS: Our results showed reasonable global and regional agreement between dDSC and other flow techniques, such as phase contrast and arterial spin labeling. CONCLUSION: In this proof-of-concept study, we demonstrated the feasibility of using transient hypoxia to generate a contrast bolus that mimics the effect of gadolinium and yields reasonable perfusion estimates. Looking forward, optimization of the hypoxia boluses and measurement of the arterial-input function is necessary to improve the accuracy of dDSC. Additionally, a cross-validation study of dDSC and DSC in brain tumor and ischemic stroke subjects is warranted to evaluate the clinical diagnostic utility of this approach.

Transient Hypoxia Model Revealed Cerebrovascular Impairment in Anemia Using BOLD MRI and Near-Infrared Spectroscopy.

BACKGROUND: Obstructive sleep apnea and nocturnal oxygen desaturations, which are prevalent in sickle cell disease (SCD) and chronic anemia disorders, have been linked to risks of stroke and silent cerebral infarcts (SCI). Cerebrovascular response to intermittent desaturations has not been well studied and may identify patients at greatest risk. PURPOSE: To investigate the cerebral dynamic response to induced desaturation in SCD patients with and without SCI, chronic anemia, and healthy subjects. STUDY TYPE: Prospective. SUBJECTS: Twenty-six SCD patients (age = 21 ± 8.2, female 46.2%), including 15 subjects without SCI and nine subjects with SCI, 15 nonsickle anemic patients (age = 22 ± 5.8, female 66.7%), and 31 controls (age = 28 ± 12.3, female 77.4%). FIELD STRENGTH/SEQUENCE: 3T, gradient-echo echo-planar imaging. ASSESSMENT: A transient hypoxia challenge of five breaths of 100% nitrogen gas was performed with blood oxygen level-dependent (BOLD) MRI and near-infrared spectroscopy (NIRS) acquisitions. Hypoxia responses were characterized by desaturation depth, time-to-peak, return-to-baseline half-life, and posthypoxia recovery in the BOLD and NIRS time courses. SCI were documented by T2 fluid-attenuation inversion recovery (FLAIR). STATISTICAL TESTS: Univariate and multivariate regressions were performed between hypoxic parameters and anemia predictors. Voxelwise two-sample t-statistic maps were used to assess the regional difference in hypoxic responses between anemic and control groups. RESULTS: Compared to controls, SCD and chronically anemic patients demonstrated significantly higher desaturation depth (P < 0.01) and shorter return-to-baseline timing response (P < 0.01). Patients having SCI had shorter time-to-peak (P < 0.01), return-to-baseline (P < 0.01), and larger desaturation depth (P < 0.01) in both white matter regions at risk and normal-appearing white matter than patients without infarcts. On multivariate analysis, desaturation depth and timing varied with age, sex, blood flow, white blood cells, and cell-free hemoglobin (r2 = 0.25 for desaturation depth; r2 = 0.18 for time-to-peak; r2 = 0.37 for return-to-baseline). DATA CONCLUSION: Transient hypoxia revealed global and regional response differences between anemic and healthy subjects. SCI was associated with extensive heterogeneity of desaturation dynamics, consistent with extensive underlying microvascular remodeling.

Resolution of neonatal posthemorrhagic ventricular dilation coincident with patent ductus arteriosus ligation: case report.

Preterm infants commonly present with a hemodynamically significant patent ductus arteriosus (hsPDA). The authors describe the case of a preterm infant with posthemorrhagic ventricular dilation, which resolved in a temporally coincident fashion to repair of hsPDA. The presence of a PDA with left-to-right shunting was confirmed at birth on echocardiogram and was unresponsive to repeated medical intervention. Initial cranial ultrasound revealed periventricular-intraventricular hemorrhage. Follow-up serial ultrasound showed resolving intraventricular hemorrhage and progressive bilateral hydrocephalus. At 5 weeks, the ductus was ligated with the goal of improving hemodynamic stability prior to CSF diversion. However, neurosurgical intervention was not required due to improvement of ventriculomegaly occurring immediately after PDA ligation. No further ventricular dilation was observed at the 6-month follow-up.Systemic venous flow disruption and abnormal patterns of cerebral blood circulation have been previously associated with hsPDA. Systemic hemodynamic change has been reported to follow hsPDA ligation, although association with ventricular normalization has not. This case suggests that the unstable hemodynamic environment due to left-to-right shunting may also impede CSF outflow and contribute to ventriculomegaly. The authors review the literature surrounding pressure transmission between a PDA and the cerebral vessels and present a mechanism by which PDA may contribute to posthemorrhagic ventricular dilation.

White matter hypointensities and hyperintensities have equivalent correlations with age and CSF ß-amyloid in the nondemented elderly.

INTRODUCTION: T1- and T2-weighted sequences from MRI often provide useful complementary information about tissue properties. Leukoaraiosis results in signal abnormalities on T1-weighted images, which are automatically quantified by FreeSurfer, but this marker is poorly characterized and is rarely used. We evaluated associations between white matter hyperintensity (WM-hyper) volume from FLAIR and white matter hypointensity (WM-hypo) volume from T1-weighted images and compared their associations with age and cerebrospinal fluid (CSF) ß-amyloid and tau. METHODS: A total of 56 nondemented participants (68-94 years) were recruited and gave informed consent. All participants went through MR imaging on a GE 1.5T scanner and of these 47 underwent lumbar puncture for CSF analysis. WM-hypo was calculated using FreeSurfer analysis of T1 FSPGR 3D, and WM-hyper was calculated with the Lesion Segmentation Toolbox in the SPM software package using T2-FLAIR. RESULTS: WM-hyper and WM-hypo were strongly correlated (r = .81; parameter estimate (p.e.): 1.53 ± 0.15; p < .0001). Age was significantly associated with both WM-hyper (r = .31, p.e. 0.078 ± 0.030, p = .013) and WM-hypo (r = .42, p.e. 0.055 ± 0.015, p < .001). CSF ß-amyloid levels were predicted by WM-hyper (r = .33, p.e. -0.11 ± 0.044, p = .013) and WM-hypo (r = .42, p.e. -0.24 ± 0.073, p = .002). CSF tau levels were not correlated with either WM-hyper (p = .9) or WM-hypo (p = .99). CONCLUSIONS: Strong correlations between WM-hyper and WM-hypo, and similar associations with age, abnormal ß-amyloid, and tau suggest a general equivalence between these two imaging markers. Our work supports the equivalence of white matter hypointensity volumes derived from FreeSurfer for evaluating leukoaraiosis. This may have particular utility when T2-FLAIR is low in quality or absent, enabling analysis of older imaging data sets.

Cerebral Lactate Concentration in Neonatal Hypoxic-Ischemic Encephalopathy: In Relation to Time, Characteristic of Injury, and Serum Lactate Concentration.

BACKGROUND: Cerebral lactate concentration can remain detectable in neonatal hypoxic-ischemic encephalopathy (HIE) after hemodynamic stability. The temporal resolution of regional cerebral lactate concentration in relation to the severity or area of injury is unclear. Furthermore, the interplay between serum and cerebral lactate in neonatal HIE has not been well defined. The study aims to describe cerebral lactate concentration in neonatal HIE in relation to time, injury, and serum lactate. DESIGN/METHODS: Fifty-two newborns with HIE undergoing therapeutic hypothermia (TH) were enrolled. Magnetic resonance imaging and spectroscopy (MRI + MR spectroscopy) were performed during and after TH at 54.6 ± 15.0 and 156 ± 57.6 h of life, respectively. Severity and predominant pattern of injury was scored radiographically. Single-voxel 1H MR spectra were acquired using short-echo (35 ms) PRESS sequence localized to the basal ganglia (BG), thalamus (Thal), gray matter (GM), and white matter. Cerebral lactate concentration was quantified by LCModel software. Serum and cerebral lactate concentrations were plotted based on age at time of measurement. Multiple comparisons of regional cerebral lactate concentration based on severity and predominant pattern of injury were performed. Spearman's Rho was computed to determine correlation between serum lactate and cerebral lactate concentration at the respective regions of interest. RESULTS: Overall, serum lactate concentration decreased over time. Cerebral lactate concentration remained low for less severe injury and decreased over time for more severe injury. Cerebral lactate remained detectable even after TH. During TH, there was a significant higher concentration of cerebral lactate at the areas of injury and also when injury was more severe. However, these differences were no longer observed after TH. There was a weak correlation between serum lactate and cerebral lactate concentration at the BG (rs = 0.3, p = 0.04) and Thal (rs = 0.35, p = 0.02). However, in infants with moderate-severe brain injury, a very strong correlation exists between serum lactate and cerebral lactate concentration at the BG (rs = 0.7, p = 0.03), Thal (rs = 0.9 p = 0.001), and GM (rs = 0.6, p = 0.04) regions. CONCLUSION: Cerebral lactate is most significantly different between regions and severity of injury during TH. There is a moderate correlation between serum and cerebral lactate concentration measured in the deep gray nuclei during TH. Differences in injury and altered regional cerebral metabolism may account for these differences.