Brain BOLD MRI O2 and CO2 stress testing: implications for perioperative neurocognitive disorder following surgery.

BACKGROUND: Mechanical ventilation to alter and improve respiratory gases is a fundamental feature of critical care and intraoperative anesthesia management. The range of inspired O2 and expired CO2 during patient management can significantly deviate from values in the healthy awake state. It has long been appreciated that hyperoxia can have deleterious effects on organs, especially the lung and retina. Recent work shows intraoperative end-tidal (ET) CO2 management influences the incidence of perioperative neurocognitive disorder (POND). The interaction of O2 and CO2 on cerebral blood flow (CBF) and oxygenation with alterations common in the critical care and operating room environments has not been well studied. METHODS: We examine the effects of controlled alterations in both ET O2 and CO2 on cerebral blood flow (CBF) in awake adults using blood oxygenation level-dependent (BOLD) and pseudo-continuous arterial spin labeling (pCASL) MRI. Twelve healthy adults had BOLD and CBF responses measured to alterations in ET CO2 and O2 in various combinations commonly observed during anesthesia. RESULTS: Dynamic alterations in regional BOLD and CBF were seen in all subjects with expected and inverse brain voxel responses to both stimuli. These effects were incremental and rapid (within seconds). The most dramatic effects were seen with combined hyperoxia and hypocapnia. Inverse responses increased with age suggesting greater risk. CONCLUSIONS: Human CBF responds dramatically to alterations in ET gas tensions commonly seen during anesthesia and in critical care. Such alterations may contribute to delirium following surgery and under certain circumstances in the critical care environment. TRIAL REGISTRATION: ClincialTrials.gov NCT02126215 for some components of the study. First registered April 29, 2014.

A clinically relevant method to screen for hepatic steatosis in overweight adolescents: a cross sectional study.

BACKGROUND: To develop a screening algorithm to detect hepatic steatosis in overweight and obese adolescents. METHODS: We performed a cross sectional study of 129 overweight adolescents 13-18 yrs. The primary outcome, hepatic steatosis was defined as an intracellular triglyceride content > 5.5 mg/g and quantified using (1)H-magenetic resonance spectroscopy. Primary predictor variables included, alanine and aspartate transaminases (ALT/AST) and features of the metabolic syndrome. RESULTS: Hepatic steatosis was present in 33% of overweight and obese adolescents. Adolescents with hepatic steatosis were more likely to be boys (adjusted OR: 4.8; 95% CI: 2.5-10.5), display a higher waist circumference (111 ± 12 vs 100 ± 13 cm, p < 0.001) and have metabolic syndrome (adjusted OR: 5.1; 95% CI: 1.6-16.4). Serum ALT predicted hepatic steatosis in boys (AUC: 0.82; 95% CI: 0.70-0.95; p < 0.001) but not girls (AUC = 0.63; 95% CI: 0.46-0.75, p = 0.16). An ALT >20 U/L, combined with the presence of metabolic syndrome, male gender and an elevated waist circumference provided the best model (AUC 0.85) with high sensitivity (72%) and specificity (82%) and positive and negative predictive values of 61% and 89% respectively. CONCLUSIONS: Serum transaminases provide modest predictive value for hepatic steatosis in youth. The ALT threshold for predicting hepatic steatosis is significantly lower than current clinical thresholds for predicting non-alcoholic fatty liver disease. The addition of ALT, presence of the metabolic syndrome and male gender significant improve the ability to predict hepatic steatosis.

Comparison of DCE-MRI parametric mapping using MP2RAGE and variable flip angle T1 mapping.

Quantitative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) measures the rate of transfer of contrast agent from the vascular space to the tissue space by fitting signal-time data to pharmacokinetic models. However, these models are very sensitive to errors in T1 mapping. Accurate T1 mapping is necessary for high quality quantitative DCE-MRI studies. This study compares magnetization prepared rapid (two) gradient echo sequence (MP2RAGE) T1-mapping accuracy to the conventional variable flip angle (VFA) approach, and also determines the effect of the new T1-mapping method on the Ktrans parameter. VFA and MP2RAGE T1 values were compared to the gold standard inverse recovery (IR) method in phantom over manually drawn ROIs. In vivo, ROIs were manually drawn over prostate and prostatic lesions. Average T1 values over ROIs were compared and Ktrans maps for each method were calculated via the extended Tofts model. VFA-T1 maps overestimated T1 values by up to 50% compared to gold standard IR T1 values in phantom. MP2RAGE differed by up to 9%. MP2RAGE-T1 and Ktrans values were significantly different from VFA values over prostatic lesions (p < 0.05). Ktrans was consistently underestimated using VFA compared to MP2RAGE (p < 0.05). MP2RAGE T1 maps are shown to be more accurate, leading to more reliable pharmacokinetic modeling. This can potentially lead to better lesion characterization and improve clinical outcomes.

Prenatal onset of the neuroradiologic phenotype of pyruvate carboxylase deficiency due to homozygous PC c.1828G > A mutations.

Pyruvate carboxylase (PC) deficiency (MIM# 266150) is an autosomal recessive disorder with three subtypes. Patients homozygous for the c.1828G > A mutation in the PC gene belong to type A, which typically has infantile onset, severe to profound developmental delay, hypotonia, and lactic acidemia. We report the neuroimaging abnormalities in a 33-week gestation infant homozygous for the c.1828G > A mutation. Brain magnetic resonance imaging on day 10 of life revealed increased T2 signal within the subcortical and periventricular white matter, an immature gyral pattern, large periventricular cysts with mass effect on the lateral ventricles, and dilatation of the occipital and temporal horns. Magnetic resonance spectroscopy showed reduced creatine and NAA peaks, a relatively high choline peak and no lactate peak. These findings were observed prior to the neonate experiencing any episodes of decompensation with lactic acidosis. The presence of these brain anomalies at this gestational age, prior to any metabolic decompensation, supports the essential role of PC in normal brain morphogenesis and the resulting in-utero brain anomalies secondary to its deficiency. Our experience with this affected premature infant and many others we have managed with the same founder mutation suggests that the clinical phenotypes of the type A and the more severe type B PC deficient patients are on a spectrum rather than distinct subtypes.

Field-map correction in read-out segmented echo planar imaging for reduced spatial distortion in prostate DWI for MRI-guided radiotherapy applications.

Diffusion-weighted echo planar imaging (DW-EPI) suffers from geometric distortion due to low phase-encoding bandwidth. Read-out segmented echo planar imaging (RS-EPI) reduces distortion but residual distortion remains in extreme cases. Additional corrections need to be applied, especially for radiotherapy applications where a high degree of accuracy is needed. In this study the use of magnetic field map corrections are assessed in DW-EPI and RS-EPI, to reduce geometric uncertainty for MRI-guided radiotherapy applications. Magnetic field maps were calculated from gradient echo images and distortion corrections were applied to RS-EPI images. Distortions were assessed in a prostate phantom by comparing to the known geometry, and in vivo using a modified Hausdorff distance metric using a T2-weighted spin echo as ground truth. Across 10 patients, field map-corrected RS-EPI reduced maximum distortion by 5 mm on average compared to DW-EPI (σ = 1.9 mm). Geometric distortions were also reduced significantly using field mapping with RS-EPI, compared to RS-EPI alone (p ≤ 0.05). The increased geometric accuracy of these techniques can potentially allow diffusion-weighted images to be fused with other MR or CT images for radiotherapy treatment purposes.

Assessing image artifacts from radiotherapy electromagnetic transponders with metal-artifact reduction imaging.

Image artifacts due to 14 gauge radiotherapy electromagnetic (EM) transponders were assessed on conventional spin echo images, and corrected using metal artifact reduction techniques: high bandwidth, view angle tilting (VAT), and slice encoding for metal artifact correction (SEMAC). Large areas of signal loss and/or pile-up were produced in an area extending up to 15.3 mm in radius for 14G transponders in standard imaging. Using high bandwidth imaging with VAT, in-plane artifact sizes were reduced by up to 35%. SEMAC did not significantly reduce in-plane or through plane artifact size for axially oriented images, but was effective in reducing through-plane artifacts for sagittal images. Using the experimental data, magnetic field maps were simulated so that the magnetic susceptibility of the transponder could be estimated and slice profiles could be visualized. Due to the large susceptibilities involved, current correction techniques are unable to fully correct artifacts due to EM transponders and significant areas of signal loss and distortion remain. Care should be taken when planning MRI following EM transponder implantation.

Blood Flow and Glucose Metabolism Dissociation in the Putamen Is Predictive of Levodopa Induced Dyskinesia in Parkinson's Disease Patients.

Background: The forefront treatment of Parkinson's disease (PD) is Levodopa. When patients are treated with Levodopa cerebral blood flow is increased while cerebral metabolic rate is decreased in key subcortical regions including the putamen. This phenomenon is especially pronounced in patients with Levodopa-induced dyskinesia (LID). Method: To study the effect of clinically-determined anti-parkinsonian medications, 10 PD patients (5 with LID and 5 without LID) have been scanned with FDG-PET (a probe for glucose metabolism) and perfusion MRI (a probe for cerebral blood flow) both when they are ON and OFF medications. Patients additionally underwent resting state fMRI to detect changes in dopamine-mediated cortico-striatal connectivity. The degree of blood flow-glucose metabolism dissociation was quantified by comparing the FDG-PET and perfusion MRI data. Results: A significant interaction effect (imaging modality × medication; blood flow-glucose metabolism dissociation) has been found in the putamen (p = 0.023). Post-hoc analysis revealed that anti-parkinsonian medication consistently normalized the pathologically hyper-metabolic state of the putamen while mixed effects were observed in cerebral blood flow changes. This dissociation was especially predominant in patients with LID compared to those without. Unlike the prior study, this differentiation was not observed when cortico-striatal functional connectivity was assessed. Conclusion: We confirmed striatal neurovascular dissociation between FDG-PET and perfusion MRI in response to clinically determined anti-parkinsonian medication. We further proposed a novel analytical method to quantify the degree of dissociation in the putamen using only the ON condition scans, Putamen-to-thalamus Hyper-perfusion/hypo-metabolism Index (PHI), which may have the potential to be used as a biomarker for LID (correctly classifying 8 out 10 patients). For wider use of PHI, a larger validation study is warranted.

Patient-Specific Alterations in CO2 Cerebrovascular Responsiveness in Acute and Sub-Acute Sports-Related Concussion.

BACKGROUND: Preliminary studies suggest that sports-related concussion (SRC) is associated with alterations in cerebral blood flow (CBF) regulation. Here, we use advanced magnetic resonance imaging (MRI) techniques to measure CBF and cerebrovascular responsiveness (CVR) in individual SRC patients and healthy control subjects. METHODS: 15 SRC patients (mean age = 16.3, range 14-20 years) and 27 healthy control subjects (mean age = 17.6, range 13-21 years) underwent anatomical MRI, pseudo-continuous arterial spin labeling (pCASL) MRI and model-based prospective end-tidal targeting (MPET) of CO2 during blood oxygenation level-dependent (BOLD) MRI. Group differences in global mean resting CBF were examined. Voxel-by-voxel group and individual differences in regional CVR were examined using statistical parametric mapping (SPM). Leave-one-out receiver operating characteristic curve analysis was used to evaluate the utility of brain MRI CO2 stress testing biomarkers to correctly discriminate between SRC patients and healthy control subjects. RESULTS: All studies were tolerated with no complications. Traumatic structural findings were identified in one SRC patient. No significant group differences in global mean resting CBF were observed. There were no significant differences in the CO2 stimulus and O2 targeting during BOLD MRI. Significant group and patient-specific differences in CVR were observed with SRC patients demonstrating a predominant pattern of increased CVR. Leave-one-out ROC analysis for voxels demonstrating a significant increase in CVR was found to reliably discriminate between SRC patients and healthy control subjects (AUC of 0.879, p = 0.0001). The optimal cutoff for increased CVR declarative for SRC was 1,899 voxels resulting in a sensitivity of 0.867 and a specificity of 0.778 for this specific ROC analysis. There was no correlation between abnormal voxel counts and Postconcussion Symptom Scale scores among SRC patients. CONCLUSION: Acute and subacute SRCs are associated with alterations in CVR that can be reliably detected by brain MRI CO2 stress testing in individual patients.

A site directed fMRI approach for evaluating functional status in the anterolateral temporal lobes.

Functional magnetic resonance imaging (fMRI) is increasingly being used for neurosurgical planning. One potential application relates to identifying eloquent cortex in regions immediately adjacent to epileptogenic foci in temporal lobe epilepsy (TLE). While medial temporal structures, such as the hippocampus and amygdala, are typically removed during surgery, it is often difficult to determine whether nearby cortical regions in the anterolateral temporal lobe should be spared. An essential first step is to identify a method of activating these regions in healthy individuals. The purpose of this study was to develop a site directed fMRI approach for evaluating functional status in the anterolateral temporal lobes. A picture-word matching task, with object category and level of abstraction factors, was used to characterize temporal lobe activation. Whole brain analysis at the group level confirmed the involvement of the temporal poles as well as adjacent superior, middle and inferior temporal gyri within a larger object recognition network. A region-of-interest analysis on the anterolateral temporal lobe demonstrated that activation varied across conditions and regions for individuals. Importantly, it was possible to detect activation in one or more conditions and/or regions for all individuals--demonstrating that it is possible to evaluate functional status. The findings provide the foundation for a novel fMRI approach in neurosurgical planning for TLE.

A Novel Stress-Diathesis Model to Predict Risk of Post-operative Delirium: Implications for Intra-operative Management.

Introduction: Risk assessment for post-operative delirium (POD) is poorly developed. Improved metrics could greatly facilitate peri-operative care as costs associated with POD are staggering. In this preliminary study, we develop a novel stress-diathesis model based on comprehensive pre-operative psychiatric and neuropsychological testing, a blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) carbon dioxide (CO2) stress test, and high fidelity measures of intra-operative parameters that may interact facilitating POD. Methods: The study was approved by the ethics board at the University of Manitoba and registered at clinicaltrials.gov as NCT02126215. Twelve patients were studied. Pre-operative psychiatric symptom measures and neuropsychological testing preceded MRI featuring a BOLD MRI CO2 stress test whereby BOLD scans were conducted while exposing participants to a rigorously controlled CO2 stimulus. During surgery the patient had hemodynamics and end-tidal gases downloaded at 0.5 hz. Post-operatively, the presence of POD and POD severity was comprehensively assessed using the Confusion Assessment Measure -Severity (CAM-S) scoring instrument on days 0 (surgery) through post-operative day 5, and patients were followed up at least 1 month post-operatively. Results: Six of 12 patients had no evidence of POD (non-POD). Three patients had POD and 3 had clinically significant confusional states (referred as subthreshold POD; ST-POD) (score ≥ 5/19 on the CAM-S). Average severity for delirium was 1.3 in the non-POD group, 3.2 in ST-POD, and 6.1 in POD (F-statistic = 15.4, p < 0.001). Depressive symptoms, and cognitive measures of semantic fluency and executive functioning/processing speed were significantly associated with POD. Second level analysis revealed an increased inverse BOLD responsiveness to CO2 pre-operatively in ST-POD and marked increase in the POD groups when compared to the non-POD group. An association was also noted for the patient population to manifest leucoaraiosis as assessed with advanced neuroimaging techniques. Results provide preliminary support for the interacting of diatheses (vulnerabilities) and intra-operative stressors on the POD phenotype. Conclusions: The stress-diathesis model has the potential to aid in risk assessment for POD. Based on these initial findings, we make some recommendations for intra-operative management for patients at risk of POD.

Deficit in schizophrenia to recruit the striatum in implicit learning: a functional magnetic resonance imaging investigation.

In schizophrenia, explicit learning deficits have been well established although it is less clear whether these patients have deficits in implicit learning (IL). IL is thought to depend on intact striatal functioning. This study examined the hypothesis that schizophrenia patients show deficient recruitment of striatal activation during an IL paradigm, relative to performance-matched healthy comparison subjects. Ten subjects with schizophrenia on atypical antipsychotic medication and 10 age, gender, education, and performance matched healthy comparison subjects underwent fMRI while performing an IL task. On the basis of whole-brain and striatal region-of-interest analyses, we found a relative lack of striatal activation in schizophrenia patients. This result is consistent with convergent evidence of striatal dysfunction in schizophrenia.

Multimodality Neurological Data Visualization With Multi-VOI-Based DTI Fiber Dynamic Integration.

Brain lesions are usually located adjacent to critical spinal structures, so it is a challenging task for neurosurgeons to precisely plan a surgical procedure without damaging healthy tissues and nerves. The advancement of medical imaging technologies produces a large amount of neurological data, which are capable of showing a wide variety of brain properties. Advanced algorithms of medical data computing and visualization are critically helpful in efficiently utilizing the acquired data for disease diagnosis and brain function and structure exploration, which is helpful for treatment planning. In this paper, we describe new algorithms and a software framework for multiple volume of interest specified diffusion tensor imaging (DTI) fiber dynamic visualization. The displayed results have been integrated with a volume rendering pipeline for multimodality neurological data exploration. A depth texture indexing algorithm is used to detect DTI fiber tracts in graphics process units (GPUs), which makes fibers to be displayed and interactively manipulated with brain data acquired from functional magnetic resonance imaging, T1- and T2-weighted anatomic imaging, and angiographic imaging. The developed software platform is built on an object-oriented structure, which is transparent and extensible. It provides a comprehensive human-computer interface for data exploration and information extraction. The GPU-accelerated high-performance computing kernels have been implemented to enable our software to dynamically visualize neurological data. The developed techniques will be useful in computer-aided neurological disease diagnosis, brain structure exploration, and general cognitive neuroscience.

Neuroimaging Assessment of Cerebrovascular Reactivity in Concussion: Current Concepts, Methodological Considerations, and Review of the Literature.

Concussion is a form of traumatic brain injury (TBI) that presents with a wide spectrum of subjective symptoms and few objective clinical findings. Emerging research suggests that one of the processes that may contribute to concussion pathophysiology is dysregulation of cerebral blood flow (CBF) leading to a mismatch between CBF delivery and the metabolic needs of the injured brain. Cerebrovascular reactivity (CVR) is defined as the change in CBF in response to a measured vasoactive stimulus. Several magnetic resonance imaging (MRI) techniques can be used as a surrogate measure of CBF in clinical and laboratory studies. In order to provide an accurate assessment of CVR, these sequences must be combined with a reliable, reproducible vasoactive stimulus that can manipulate CBF. Although CVR imaging currently plays a crucial role in the diagnosis and management of many cerebrovascular diseases, only recently have studies begun to apply this assessment tool in patients with concussion. In order to evaluate the quality, reliability, and relevance of CVR studies in concussion, it is important that clinicians and researchers have a strong foundational understanding of the role of CBF regulation in health, concussion, and more severe forms of TBI, and an awareness of the advantages and limitations of currently available CVR measurement techniques. Accordingly, in this review, we (1) discuss the role of CVR in TBI and concussion, (2) examine methodological considerations for MRI-based measurement of CVR, and (3) provide an overview of published CVR studies in concussion patients.

Longitudinal Brain Magnetic Resonance Imaging CO2 Stress Testing in Individual Adolescent Sports-Related Concussion Patients: A Pilot Study.

BACKGROUND: Advanced neuroimaging studies in concussion have been limited to detecting group differences between concussion patients and healthy controls. In this small pilot study, we used brain magnetic resonance imaging (MRI) CO2 stress testing to longitudinally assess cerebrovascular responsiveness (CVR) in individual sports-related concussion (SRC) patients. METHODS: Six SRC patients (three males and three females; mean age = 15.7, range = 15-17 years) underwent longitudinal brain MRI CO2 stress testing using blood oxygen level-dependent (BOLD) MRI and model-based prospective end-tidal CO2 targeting under isoxic conditions. First-level and second-level comparisons were undertaken using statistical parametric mapping (SPM) to score the scans and compare them to an atlas of 24 healthy control subjects. RESULTS: All tests were well tolerated and without any serious adverse events. Anatomical MRI was normal in all study participants. The CO2 stimulus was consistent between the SRC patients and control subjects and within SRC patients across the longitudinal study. Individual SRC patients demonstrated both quantitative and qualitative patient-specific alterations in CVR (p < 0.005) that correlated strongly with clinical findings, and that persisted beyond clinical recovery. CONCLUSION: Standardized brain MRI CO2 stress testing is capable of providing a longitudinal assessment of CVR in individual SRC patients. Consequently, larger prospective studies are needed to examine the utility of brain MRI CO2 stress testing as a clinical tool to help guide the evaluation, classification, and longitudinal management of SRC patients.

Brain magnetic resonance imaging CO2 stress testing in adolescent postconcussion syndrome.

OBJECT A neuroimaging assessment tool to visualize global and regional impairments in cerebral blood flow (CBF) and cerebrovascular responsiveness in individual patients with concussion remains elusive. Here the authors summarize the safety, feasibility, and results of brain CO2 stress testing in adolescents with postconcussion syndrome (PCS) and healthy controls. METHODS This study was approved by the Biomedical Research Ethics Board at the University of Manitoba. Fifteen adolescents with PCS and 17 healthy control subjects underwent anatomical MRI, pseudo-continuous arterial spin labeling MRI, and brain stress testing using controlled CO2 challenge and blood oxygen level-dependent (BOLD) MRI. Post hoc processing was performed using statistical parametric mapping to determine voxel-by-voxel regional resting CBF and cerebrovascular responsiveness of the brain to the CO2 stimulus (increase in BOLD signal) or the inverse (decrease in BOLD signal). Receiver operating characteristic (ROC) curves were generated to compare voxel counts categorized by control (0) or PCS (1). RESULTS Studies were well tolerated without any serious adverse events. Anatomical MRI was normal in all study participants. No differences in CO2 stimuli were seen between the 2 participant groups. No group differences in global mean CBF were detected between PCS patients and healthy controls. Patient-specific differences in mean regional CBF and CO2 BOLD responsiveness were observed in all PCS patients. The ROC curve analysis for brain regions manifesting a voxel response greater than and less than the control atlas (that is, abnormal voxel counts) produced an area under the curve of 0.87 (p < 0.0001) and 0.80 (p = 0.0003), respectively, consistent with a clinically useful predictive model. CONCLUSIONS Adolescent PCS is associated with patient-specific abnormalities in regional mean CBF and BOLD cerebrovascular responsiveness that occur in the setting of normal global resting CBF. Future prospective studies are warranted to examine the utility of brain MRI CO2 stress testing in the longitudinal assessment of acute sports-related concussion and PCS.

Pancreatic lipid content is not associated with beta cell dysfunction in youth-onset type 2 diabetes.

OBJECTIVE: To determine whether pancreatic lipid content is associated with type 2 diabetes and beta cell function in Indigenous and Caucasian adolescents. METHODS: This was a cross-sectional study comparing (1)H-magnetic resonance spectroscopy-derived pancreatic triglyceride content in adolescents 13 to 18 years of age with type 2 diabetes (n=20) and body mass index-matched normoglycemic controls (n=34). Beta cell function was measured by the acute insulin response and disposition index derived from intravenous glucose tolerance tests. RESULTS: Pancreatic lipid content was not significantly different in youth with type 2 diabetes and their normoglycemic body mass index-matched peers (2.41 [95% CI: 0.63, 5.60] vs. 1.22 [0.08, 5.93]; p=0.27). Pancreatic triglyceride levels were not associated with measures of beta cell function in the cohort. In subgroup analyses, pancreatic lipid content was ∼4-fold higher in youth with type 2 diabetes who were carriers of the G319S mutation in the HNF-1alpha gene (7.45 [2.85, 26.8] vs. 2.20 [0.350, 3.30] % Fat to Water Ratio F/W; p=0.032). CONCLUSIONS: Pancreatic lipid content is not elevated in Indigenous or Caucasian youth with type 2 diabetes compared to normoglycemic youth, nor is it associated with beta cell function. The presence of the G319S mutation in the HNF-1alpha gene in Indigenous youth with type 2 diabetes is associated with higher pancreatic lipid content. Further research is needed to understand the mechanisms that explain beta cell failure in overweight youth with type 2 diabetes.

The fan effect in fMRI: left hemisphere specialization in verbal working memory.

We studied the fan effect of verbal working memory using functional magnetic resonance imaging (fMRI). Participants were presented with a sentence-pair matching task that described semantic relationships (e.g. classroom-school). Working memory load and semantic processing were manipulated by increasing the number of sentences to be remembered and varying whether they matched expectation. Increased working memory load elicited activation in left dorsal frontal and left inferior parietal regions, and also delayed the hemodynamic responses. Convergent results from semantic matches occurred in the left parietal lobe, whereas, left ventral frontal activation from mismatches diverged from working memory results. The findings were consistent with behavioural and electrophysiological evidence, with the fan effect in fMRI providing novel insight into the spatiotemporal nature of verbal working memory in the left hemisphere.

Brain MRI CO2 stress testing: a pilot study in patients with concussion.

BACKGROUND: There is a real need for quantifiable neuro-imaging biomarkers in concussion. Here we outline a brain BOLD-MRI CO2 stress test to assess the condition. METHODS: This study was approved by the REB at the University of Manitoba. A group of volunteers without prior concussion were compared to post-concussion syndrome (PCS) patients--both symptomatic and recovered asymptomatic. Five 3-minute periods of BOLD imaging at 3.0 T were studied--baseline 1 (BL1--at basal CO2 tension), hypocapnia (CO2 decreased ∼5 mmHg), BL2, hypercapnia (CO2 increased ∼10 mmHg) and BL3. Data were processed using statistical parametric mapping (SPM) for 1st level analysis to compare each subject's response to the CO2 stress at the p = 0.001 level. A 2nd level analysis compared each PCS patient's response to the mean response of the control subjects at the p = 0.05 level. RESULTS: We report on 5 control subjects, 8 symptomatic and 4 asymptomatic PCS patients. Both increased and decreased response to CO2 was seen in all PCS patients in the 2nd level analysis. The responses were quantified as reactive voxel counts: whole brain voxel counts (2.0±1.6%, p = 0.012 for symptomatic patients for CO2 response < controls and 3.0±5.1%, p = 0.139 for CO2 response > controls: 0.49±0.31%, p = 0.053 for asymptomatic patients for CO2 response < controls and 4.4±6.8%, p = 0.281 for CO2 response > controls). CONCLUSIONS: Quantifiable alterations in regional cerebrovascular responsiveness are present in concussion patients during provocative CO2 challenge and BOLD MRI and not in healthy controls. Future longitudinal studies must aim to clarify the relationship between CO2 responsiveness and individual patient symptoms and outcomes.

Dietary determinants of hepatic steatosis and visceral adiposity in overweight and obese youth at risk of type 2 diabetes.

BACKGROUND: Dietary determinants of hepatic steatosis, an important precursor for nonalcoholic fatty liver disease, are undefined. OBJECTIVE: We explored the roles of sugar and fat intake as determinants of hepatic steatosis and visceral obesity in overweight adolescents at risk of type 2 diabetes. DESIGN: This was a cross-sectional study of dietary patterns and adipose tissue distribution in 74 overweight adolescents (aged: 15.4 ± 1.8 y; body mass index z score: 2.2 ± 0.4). Main outcome measures were hepatic steatosis (≥5.5% fat:water) measured by magnetic resonance spectroscopy and visceral obesity (visceral-to-subcutaneous adipose tissue ratio ≥0.25) measured by magnetic resonance imaging. Main exposure variables were dietary intake and habits assessed by the Harvard Youth Adolescent Food Frequency Questionnaire. RESULTS: Hepatic steatosis and visceral obesity were evident in 43% and 44% of the sample, respectively. Fried food consumption was more common in adolescents with hepatic steatosis than in adolescents without hepatic steatosis (41% compared with 18%; P = 0.04). Total fat intake (ß = 0.51, P = 0.03) and the consumption of >35% of daily energy intake from fat (OR: 11.8; 95% CI: 1.6, 86.6; P = 0.02) were both positively associated with hepatic steatosis. Available carbohydrate (ß = 0.54, P = 0.02) and the frequent consumption of soda were positively associated with visceral obesity (OR: 6.4; 95% CI: 1.2, 34.0; P = 0.03). Daily fiber intake was associated with reduced odds of visceral obesity (OR: 0.82; 95% CI: 0.68, 0.98; P = 0.02) but not hepatic steatosis. CONCLUSION: Hepatic steatosis is associated with a greater intake of fat and fried foods, whereas visceral obesity is associated with increased consumption of sugar and reduced consumption of fiber in overweight and obese adolescents at risk of type 2 diabetes.

Synchronized 2D/3D optical mapping for interactive exploration and real-time visualization of multi-function neurological images.

Efficient software with the ability to display multiple neurological image datasets simultaneously with full real-time interactivity is critical for brain disease diagnosis and image-guided planning. In this paper, we describe the creation and function of a new comprehensive software platform that integrates novel algorithms and functions for multiple medical image visualization, processing, and manipulation. We implement an opacity-adjustment algorithm to build 2D lookup tables for multiple slice image display and fusion, which achieves a better visual result than those of using VTK-based methods. We also develop a new real-time 2D and 3D data synchronization scheme for multi-function MR volume and slice image optical mapping and rendering simultaneously through using the same adjustment operation. All these methodologies are integrated into our software framework to provide users with an efficient tool for flexibly, intuitively, and rapidly exploring and analyzing the functional and anatomical MR neurological data. Finally, we validate our new techniques and software platform with visual analysis and task-specific user studies.