Quantitative BOLD (qBOLD) imaging of oxygen metabolism and blood oxygenation in the human body: A scoping review.

PURPOSE: There are many approaches to the quantitative BOLD (qBOLD) technique described in the literature, differing in pulse sequences, MRI parameters and data processing. Thus, in this review, we summarized the acquisition methods, approaches used for oxygenation quantification and clinical populations investigated. METHODS: Three databases were systematically searched (Medline, Embase, and Web of Science) for published research that used qBOLD methods for quantification of oxygen metabolism. Data extraction and synthesis were performed by one author and reviewed by a second author. RESULTS: A total of 93 relevant papers were identified. Acquisition strategies were summarized, and oxygenation parameters were found to have been investigated in many pathologies such as steno-occlusive diseases, stroke, glioma, and multiple sclerosis disease. CONCLUSION: A summary of qBOLD approaches for oxygenation measurements and applications could help researchers to identify good practice and provide objective information to inform the development of future consensus recommendations.

Oxygen extraction fraction (OEF) values and applications in neurological diseases.

One of the goals of this systematic review is to provide a meta-analysis-derived mean OEF of healthy volunteers. Another aim of this study is to indicate the OEF ranges of various neurological pathologies. Potential clinical applications of OEF metrics are presented. Peer-reviewed studies reporting OEF metrics derived from computed tomography (CT)/positron emission tomography (PET) and/or magnetic resonance imaging (MRI) were considered. Databases utilized included MEDLINE, PubMed, EMBASE, Web of Science, and Google Scholar. The Newcastle-Ottawa scoring system was used for evaluating studies. R Studio was utilized for the meta-analysis calculations when appropriate. The GRADE framework was utilized to assess additional findings. Of 2267 potential studies, 165 met the inclusion criteria. The healthy volunteer meta-analysis included 339 subjects and found a mean OEF value of 38.87 (37.38, 40.36), with a prediction interval of 32.40-45.34. There were no statistical differences in OEF values derived from PET versus MRI. We provided a GRADE A certainty rating for the use of OEF metrics to predict stroke occurrence in patients with symptomatic carotid or cerebral vessel disease. We provided a GRADE B certainty rating for monitoring treatment response in Moyamoya disease. Use of OEF metrics in diagnosing and/or monitoring other conditions had a GRADE C certainty rating or less. OEF might have a role in diagnosing and monitoring patients with symptomatic carotid or cerebral vessel disease and Moyamoya disease. While we found insufficient evidence to support measuring OEF metrics in other patient populations, in many cases, further studies are warranted.

Cerebral oxygen extraction fraction: Comparison of dual-gas challenge calibrated BOLD with CBF and challenge-free gradient echo QSM+qBOLD.

PURPOSE: To compare cortical gray matter oxygen extraction fraction (OEF) estimated from 2 MRI methods: (1) the quantitative susceptibility mapping (QSM) plus quantitative blood oxygen level dependent imaging (qBOLD) (QSM+qBOLD or QQ), and (2) the dual-gas calibrated-BOLD (DGCB) in healthy subjects; and to investigate the validity of iso-cerebral metabolic rate of oxygen consumption assumption during hypercapnia using QQ. METHODS: In 10 healthy subjects, 3 tesla MRI including a multi-echo gradient echo sequence at baseline and hypercapnia for QQ, as well as an EPI dual-echo pseudo-continuous arterial spin labeling for DGCB, were performed under a hypercapnic and a hyperoxic condition. OEFs from QQ and DGCB were compared using region of interest analysis and paired t test. For QQ, cerebral metabolic rate of oxygen consumption = cerebral blood flow*OEF*arterial oxygen content was generated for both baseline and hypercapnia, which were compared. RESULTS: Average OEF in cortical gray matter across 10 subjects from QQ versus DGCB was 35.5 ± 6.7% versus 38.0 ± 9.1% (P = .49) at baseline and 20.7 ± 4.4% versus 28.4 ± 7.6% (P = .02) in hypercapnia: OEF in cortical gray matter was significantly reduced as measured in QQ (P < .01) and in DGCB (P < .01). Cerebral metabolic rate of oxygen consumption (in µmol O2 /min/100 g) was 168.2 ± 54.1 at baseline from DGCB and was 153.1 ± 33.8 at baseline and 126.4 ± 34.2 (P < .01) in hypercapnia from QQ. CONCLUSION: The differences in OEF obtained from QQ and DGCB are small and nonsignificant at baseline but are statistically significant during hypercapnia. In addition, QQ shows a cerebral metabolic rate of oxygen consumption decrease (17.4%) during hypercapnia.

Assessment of odour emissions by the use of a dispersion model in the context of the proposed new law in Chile.

Chile is looking to define a regulatory framework for the odour emissions of various critical industrial activities. One of these is the sanitary sector, with 300 wastewater treatment plants (WWTP). The basis currently used by the Chilean environmental authority to assess odours is the set of odour emission factors (OEF) taken from the Dutch standard. The aim of this study was to compare these, used as a national reference, with our own OEF calculated from measurements using dynamic olfactometry of 41 WWTP. The dependence of OEF on operational variables such as flow rate and BOD5 was analysed in different plant processes. The current regulations were assessed under the two OEF scenarios for the 95th, 98th and 99.9th percentiles in the Temuco WWTP, using the WRF-CALPUFF modelling protocol. The OEF values of the emission sources showed no strong correlation with operating variables like BOD5 and wastewater flow rates in all plant sections. Our OEF values based on real measurements presented significant differences from the Dutch reference OEF, of the order of 6 UOe/m2/s. The odour emitting-units with the largest differences were the pre-treatment units, flow-splitting chamber and most units of the sludge processing sections. These new OEF offer an alternative paradigm for measuring emissions and an incentive to more accurate calculation of the emissions in critical units such as sludge treatment lines. When the WWTP studied in Temuco was assessed using the OEF calculated in this study, a difference of 1041 OUe/s was found above the odours emissions calculated using the Dutch reference database. Using the Dutch OEF, the odour immission concentrations at nearby receptors were not exceeded for the 95th and 98th percentiles; this might result in deficient environmental assessment under current Chilean laws. We therefore recommend that Chilean institutions should assess projects using the OEF calculated in this study.

Oxygen extraction fraction mapping with multi-parametric quantitative BOLD MRI: Reduced transverse relaxation bias using 3D-GraSE imaging.

Magnetic resonance imaging (MRI)-based quantification of the blood-oxygenation-level-dependent (BOLD) effect allows oxygen extraction fraction (OEF) mapping. The multi-parametric quantitative BOLD (mq-BOLD) technique facilitates relative OEF (rOEF) measurements with whole brain coverage in clinically applicable scan times. Mq-BOLD requires three separate scans of cerebral blood volume and transverse relaxation rates measured by gradient-echo (1/T2∗) and spin-echo (1/T2). Although the current method is of clinical merit in patients with stroke, glioma and internal carotid artery stenosis (ICAS), there are relaxation measurement artefacts that impede the sensitivity of mq-BOLD and artificially elevate reported rOEF values. We posited that T2-related biases caused by slice refocusing imperfections during rapid 2D-GraSE (Gradient and Spin Echo) imaging can be reduced by applying 3D-GraSE imaging sequences, because the latter requires no slice selective pulses. The removal of T2-related biases would decrease overestimated rOEF values measured by mq-BOLD. We characterized effects of T2-related bias in mq-BOLD by comparing the initially employed 2D-GraSE and two proposed 3D-GraSE sequences to multiple single spin-echo reference measurements, both in vitro and in vivo. A phantom and 25 participants, including young and elderly healthy controls as well as ICAS-patients, were scanned. We additionally proposed a procedure to reliably identify and exclude artefact affected voxels. In the phantom, 3D-GraSE derived T2 values had 57% lower deviation from the reference. For in vivo scans, the formerly overestimated rOEF was reduced by -27% (p â€‹< â€‹0.001). We obtained rOEF â€‹= â€‹0.51, which is much closer to literature values from positron emission tomography (PET) measurements. Furthermore, increased sensitivity to a focal rOEF elevation in an ICAS-patient was demonstrated. In summary, the application of 3D-GraSE improves the mq-BOLD-based rOEF quantification while maintaining clinically feasible scan times. Thus, mq-BOLD with non-slice selective T2 imaging is highly promising to improve clinical diagnostics of cerebrovascular diseases such as ICAS.

Quantification of whole-brain oxygenation extraction fraction and cerebral metabolic rate of oxygen consumption in adults with sickle cell anemia using individual T2 -based oxygenation calibrations.

PURPOSE: To evaluate different T2 -oxygenation calibrations for estimating venous oxygenation in people with sickle cell anemia (SCA). METHODS: Blood T2 values were measured at 3 T in the internal jugular veins of 12 healthy volunteers and 11 SCA participants with no history of stroke, recent transfusion, or renal impairment. T2 -oxygenation relationships of both sickled and normal blood samples were calibrated individually and compared with values generated from published models. After converting venous T2 values to venous oxygenation, whole-brain oxygen extraction fraction and cerebral metabolic rate of oxygen were calculated. RESULTS: Sickle blood samples' oxygenation values calculated from our individual calibrations agreed well with measurements using a blood analyzer, whereas previous T2 calibrations based on normal blood samples showed 13%-19% underestimation. Meanwhile, oxygenation values calculated from previous grouped T2 calibration for sickle blood agreed well with experimental measurement on averaged values, but showed up to 20% variation for several individual samples. Using individual T2 calibrations, the whole-brain oxygen extraction fraction and cerebral metabolic rate of oxygen of SCA participants were 0.38 ± 0.08 and 172 ± 42 µmol/min/100 g, respectively, which were comparable to those values measured on healthy volunteers. CONCLUSION: Our results confirm that sickle blood T2 values not only depend on the hematocrit and oxygenation values, but also on other hematological factors. The individual T2 calibrations minimized the effect of heterogeneity of sickle blood between different SCA populations and improved the accuracy of T2 -based oximetry. The measured oxygen extraction fraction and cerebral metabolic rate of oxygen of this group of SCA participants were found to not differ significantly from those of healthy individuals.

Detecting resting-state brain activity using OEF-weighted imaging.

Traditional resting-state functional magnetic resonance imaging (fMRI) is mainly based on the blood oxygenation level-dependent (BOLD) contrast. The oxygen extraction fraction (OEF) represents an important parameter of brain metabolism and is a key biomarker of tissue viability, detecting the ratio of oxygen utilization to oxygen delivery. Investigating spontaneous fluctuations in the OEF-weighted signal is crucial for understanding the underlying mechanism of brain activity because of the immense energy budget during the resting state. However, due to the poor temporal resolution of OEF mapping, no studies have reported using OEF contrast to assess resting-state brain activity. In this fMRI study, we recorded brain OEF-weighted fluctuations for 10 min in healthy volunteers across two scanning visits, using our recently developed pulse sequence that can acquire whole-brain voxel-wise OEF-weighted signals with a temporal resolution of 3 s. Using both group-independent component analysis and seed-based functional connectivity analysis, we robustly identified intrinsic brain networks, including the medial visual, lateral visual, auditory, default mode and bilateral executive control networks, using OEF contrast. Furthermore, we investigated the resting-state local characteristics of brain activity based on OEF-weighted signals using regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF). We demonstrated that the gray matter regions of the brain, especially those in the default mode network, showed higher ReHo and fALFF values with the OEF contrast. Moreover, voxel-wise test-retest reliability comparisons across the whole brain demonstrated that the reliability of resting-state brain activity based on the OEF contrast was moderate for the network indices and high for the local activity indices, especially for ReHo. Although the reliabilities of the OEF-based indices were generally lower than those based on BOLD, the reliability of OEF-ReHo was slightly higher than that of BOLD-ReHo, with a small effect size, which indicated that OEF-ReHo could be used as a reliable index for characterizing resting-state local brain activity as a complement to BOLD. In conclusion, OEF can be used as an effective contrast to study resting-state brain activity with a medium to high test-retest reliability.

Calibrated fMRI for mapping absolute CMRO2: Practicalities and prospects.

Functional magnetic resonance imaging (fMRI) is an essential workhorse of modern neuroscience, providing valuable insight into the functional organisation of the brain. The physiological mechanisms underlying the blood oxygenation level dependent (BOLD) effect are complex and preclude a straightforward interpretation of the signal. However, by employing appropriate calibration of the BOLD signal, quantitative measurements can be made of important physiological parameters including the absolute rate of cerebral metabolic oxygen consumption or oxygen metabolism (CMRO2) and oxygen extraction (OEF). The ability to map such fundamental parameters has the potential to greatly expand the utility of fMRI and to broaden its scope of application in clinical research and clinical practice. In this review article we discuss some of the practical issues related to the calibrated-fMRI approach to the measurement of CMRO2. We give an overview of the necessary precautions to ensure high quality data acquisition, and explore some of the pitfalls and challenges that must be considered as it is applied and interpreted in a widening array of diseases and research questions.

Risk Factors of Obesity in Veterans of Recent Conflicts: Need for Diabetes Prevention.

PURPOSE OF REVIEW: To identify factors associated with obesity in veterans of the recent, Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) war conflicts. RECENT FINDINGS: Over 44% OEF/OIF/OND veterans are obese (BMI > 30 kg/m2), which exceeds the national obesity prevalence rate of 39% in people younger than 45. Obesity increases morbidity, risk for type 2 diabetes (T2D), and mortality as well as decreases quality of life. A scoping review method was used to identify factors associated with obesity in young veterans. Military exposures, such as multiple deployments and exposure to combat, contribute to challenges in re-integration to civilian life in all veterans. Factors that contribute to increased risk for obesity include changes in eating patterns/eating disorders, changes in physical activity, physical disability, and psychological comorbidity. These conditions can contribute to a rapid weight gain trajectory, changes in metabolism, and obesity. Young veterans face considerable challenges related to obesity risk. Further research is needed to better understand young veterans' experiences and health needs in order to adapt or expand existing programs and improve access, engagement, and metabolic outcomes in this vulnerable population.

Cerebral revascularization after the Carotid Occlusion Surgery Study: what candidates remain, and can we do better?

OBJECTIVECerebral revascularization for carotid occlusion was previously a mainstay procedure for the cerebrovascular neurosurgeon. However, the 1985 extracranial-intracranial bypass trial and subsequently the Carotid Occlusion Surgery Study (COSS) provided level 1 evidence via randomized controlled trials against bypass for symptomatic atherosclerotic carotid occlusion disease. However, in a small number of patients optimal medical therapy fails, and some patients with flow-limiting stenosis develop a perfusion-dependent neurological examination. Therefore it is necessary to further stratify patients by risk to determine who may most benefit from this intervention as well as to determine perioperative morbidity in this high-risk patient population.METHODSA retrospective review was performed of all revascularization procedures done for symptomatic atherosclerotic cerebrovascular steno-occlusive disease. All patients undergoing revascularization after the publication of the COSS in 2011 were included. Perioperative morbidity and mortality were assessed as the primary outcome to determine safety of revascularization in this high-risk population. All patients had documented hypoperfusion on hemodynamic imaging.RESULTSAt total of 35 revascularization procedures were included in this review. The most common indication was for patients with recurrent strokes, who were receiving optimal medical therapy and who suffered from cerebrovascular steno-occlusion. At 30 days only 3 perioperative ischemic events were observed, 2 of which led to no long-term neurological deficit. Immediate graft patency was good, at 94%. Long term, no further strokes or ischemic events were observed, and graft patency remained high at 95%. There were no factors associated with perioperative ischemic events in the variables that were recorded.CONCLUSIONSCerebral revascularization may be done safely at high-volume cerebrovascular centers in high-risk patients in whom optimal medical therapy has failed. Further research must be done to develop an improved methodology of risk stratification for patients with symptomatic atherosclerotic cerebrovascular steno-occlusive disease to determine which patients may benefit from intervention. Given the high risk of recurrent stroke in certain patients, and the fact that patients fail medical therapy, surgical revascularization may provide the best method to ensure good long-term outcomes with manageable up-front risks.

Contemporary and emerging magnetic resonance imaging methods for evaluation of moyamoya disease.

Numerous recent technological advances offer the potential to substantially enhance the MRI evaluation of moyamoya disease (MMD). These include high-resolution volumetric imaging, high-resolution vessel wall characterization, improved cerebral angiographic and perfusion techniques, high-field imaging, fast scanning methods, and artificial intelligence. This review discusses the current state-of-the-art MRI applications in these realms, emphasizing key imaging findings, clinical utility, and areas that will benefit from further investigation. Although these techniques may apply to imaging of a wide array of neurovascular or other neurological conditions, consideration of their application to MMD is useful given the comprehensive multidimensional MRI assessment used to evaluate MMD. These MRI techniques span from basic cross-sectional to advanced functional sequences, both qualitative and quantitative.The aim of this review was to provide a comprehensive summary and analysis of current key relevant literature of advanced MRI techniques for the evaluation of MMD with image-rich case examples. These imaging methods can aid clinical characterization, help direct treatment, assist in the evaluation of treatment response, and potentially improve the understanding of the pathophysiology of MMD.

Accounting for the role of hematocrit in between-subject variations of MRI-derived baseline cerebral hemodynamic parameters and functional BOLD responses.

Baseline hematocrit fraction (Hct) is a determinant for baseline cerebral blood flow (CBF) and between-subject variation of Hct thus causes variation in task-based BOLD fMRI signal changes. We first verified in healthy volunteers (n = 12) that Hct values can be derived reliably from venous blood T1 values by comparison with the conventional lab test. Together with CBF measured using phase-contrast MRI, this noninvasive estimation of Hct, instead of using a population-averaged Hct value, enabled more individual determination of oxygen delivery (DO2 ), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2 ). The inverse correlation of CBF and Hct explained about 80% of between-subject variation of CBF in this relatively uniform cohort of subjects, as expected based on the regulation of DO2 to maintain constant CMRO2 . Furthermore, we compared the relationships of visual task-evoked BOLD response with Hct and CBF. We showed that Hct and CBF contributed 22%-33% of variance in BOLD signal and removing the positive correlation with Hct and negative correlation with CBF allowed normalization of BOLD signal with 16%-22% lower variability. The results of this study suggest that adjustment for Hct effects is useful for studies of MRI perfusion and BOLD fMRI. Hum Brain Mapp 39:344-353, 2018. © 2017 Wiley Periodicals, Inc.

Quantitative susceptibility mapping-based cerebral metabolic rate of oxygen mapping with minimum local variance.

PURPOSE: The objective of this study was to demonstrate the feasibility of a cerebral metabolic rate of oxygen (CMRO2 ) mapping method based on its minimum local variance (MLV) without vascular challenge using quantitative susceptibility mapping (QSM) and cerebral blood flow (CBF). METHODS: Three-dimensional multi-echo gradient echo imaging and arterial spin labeling were performed in 11 healthy subjects to calculate QSM and CBF. Minimum local variance was used to compute whole-brain CMRO2 map from QSM and CBF. The MLV method was compared with a reference method using the caffeine challenge. Their agreement within the cortical gray matter (CGM) was assessed on CMRO2 and oxygen extraction fraction (OEF) maps at both baseline and challenge states. RESULTS: Mean CMRO2 (in µmol/100 g/min) obtained in CGM using the caffeine challenge and MLV were 142 ± 16.5 and 139 ± 14.8 µmol/100 g/min, respectively; the corresponding baseline OEF were 33.0 ± 4.0% and 31.8 ± 3.2%, respectively. The MLV and caffeine challenge methods showed no statistically significant differences across subjects with small ( < 4%) biases in CMRO2 and OEF values. CONCLUSIONS: Minimum local variance-based CMRO2 mapping without vascular challenge using QSM and arterial spin labeling is feasible in healthy subjects. Magn Reson Med 79:172-179, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Functional Brain Alterations Associated With Cognitive Control in Blast-Related Mild Traumatic Brain Injury.

OBJECTIVES: Research on the cognitive sequelae of mild traumatic brain injury (mTBI) suggests that, despite generally rapid recovery, difficulties may persist in the domain of cognitive control. The goal of this study was to examine whether individuals with chronic blast-related mTBI show behavioral or neural alterations associated with cognitive control. METHODS: We collected event-related functional magnetic resonance imaging (fMRI) data during a flanker task in 17 individuals with blast-related mTBI and 16 individuals with blast-exposure without TBI (control). RESULTS: Groups did not significantly differ in behavioral measures of cognitive control. Relative to the control group, the mTBI group showed greater deactivation of regions associated with the default mode network during the processing of errors. Additionally, error processing in the mTBI group was associated with enhanced negative coupling between the default mode network and the dorsal anterior cingulate cortex as well as the dorsolateral prefrontal cortex, regions of the salience and central executive networks that are associated with cognitive control. CONCLUSIONS: These results suggest that deactivation of default mode network regions and associated enhancements of connectivity with cognitive control regions may act as a compensatory mechanism for successful cognitive control task performance in mTBI. (JINS, 2018, 24, 662-672).

Continuum of the United States military's traumatic brain injury care: adjusting to the changing battlefield.

Over the past 8 years, advances in the US Military Health System (MHS) have led to extensive changes in the way combat casualty care is provided to deployed service members with a traumatic brain injury (TBI). Changes include the application of cutting-edge Clinical Practice Guidelines, use of pioneering technologies, and advances in evacuation procedures. Compared with previous engagements, current operations occur on a much smaller scale, and more frequently in austere environments, such that effective medical support is increasingly challenging. In this paper, the authors describe key aspects of the current continuum of TBI care in the US military, from the point of injury through rehabilitation, with an emphasis on how emerging technologies and evidence-based Clinical Practice Guidelines assist MHS clinicians with providing the best clinical care possible in the changing battlefield.

Complexity of the Relationships of Pain, Posttraumatic Stress, and Depression in Combat-Injured Populations: An Integrative Review to Inform Evidence-Based Practice.

BACKGROUND: Understanding the complex interrelationships between combat injuries, physical health, and mental health symptoms is critical to addressing the healthcare needs of wounded military personnel and veterans. The relationship between injury characteristics, pain, posttraumatic stress disorder (PTSD), and depression among combat-injured military personnel is unique to modern conflicts and understudied in the nursing literature. AIM: This integrative review synthesizes clinical presentations and relationships of combat injury, PTSD, depression, and pain in Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) United States military service members and veterans. METHODS: A literature search was conducted using relative key terms across databases to identify peer-reviewed publications between 2001 and 2016 that examined health outcomes of combat-injured persons in OEF and OIF. The quality of evidence was evaluated and results synthesized to examine the association of combat injury as a risk factor for PTSD, the relationship of PTSD and depression pre- and postinjury, and pain management throughout care. RESULTS: Twenty-two articles were included in this review. Greater injury and pain severity poses risks for developing PTSD following combat injury, while early symptom management lessens risks for PTSD. Depression appears to be both a contributing risk factor to postinjury PTSD, as well as a comorbidity. LINKING EVIDENCE TO ACTION: Findings demonstrate a compelling need for improvements in standardized assessment of pain and mental health symptoms across transitions in care. This integrative review informs nurse researchers and providers of the clinical characteristics of pain, PTSD, and depression following combat injury and offers implications for future research promoting optimal surveillance of symptoms.

Cerebral metabolic rate of oxygen (CMRO2 ) mapping with hyperventilation challenge using quantitative susceptibility mapping (QSM).

PURPOSE: Our objective was to demonstrate the feasibility of using hyperventilation as an efficient vasoconstrictive challenge and prior knowledge as denoising constraints for cerebral metabolic rate of oxygen (CMRO2 ) mapping based upon quantitative susceptibility mapping (QSM). METHODS: Three-dimensional (3D) multi-echo gradient echo and arterial spin labeling imaging were performed to calculate QSM and perfusion maps before and after a hyperventilation challenge in 11 healthy subjects. For comparison, this was repeated using a caffeine challenge. Whole-brain CMRO2 and oxygen extraction fraction (OEF) maps were computed using constrained optimization. Hyperventilation scans were repeated to measure reproducibility. Regional agreement of CMRO2 and OEF maps was analyzed within the cortical gray matter (CGM) using t-test and Bland-Altman plots. RESULTS: Hyperventilation challenge eliminates the 30-min waiting time needed for caffeine to exert its vasoconstrictive effects. Mean CMRO2 (in µmol/100g/min) obtained in CGM using the caffeine and repeated hyperventilation scans were 149 ± 16, 153 ± 19, and 150 ± 20, respectively. This corresponded to an OEF of 33.6 ± 3.4%, 32.3 ± 3.2%, and 34.1 ± 3.8% at baseline state and 39.8 ± 4.8%, 43.6 ± 6.2%, and 42.8 ± 6.8% at challenged state, respectively. Hyperventilation scans produced a good agreement of CMRO2 and OEF values. CONCLUSIONS: Hyperventilation is a feasible, reproducible, and efficient vasoconstrictive challenge for QSM-based quantitative CMRO2 mapping. Magn Reson Med 77:1762-1773, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Reliable estimation of microvascular flow patterns in patients with disrupted blood-brain barrier using dynamic susceptibility contrast MRI.

PURPOSE: To present and quantify the performance of a method to compute tissue hemodynamic parameters from dynamic susceptibility contrast (DSC) MRI data in brain tissue with possible nonintact blood-brain barrier. THEORY AND MATERIALS AND METHODS: We propose a Bayesian scheme to obtain perfusion metrics, including capillary transit-time heterogeneity (CTH), from DSC-MRI data in the presence of contrast agent extravasation. Initial performance assessment is performed through simulations. Next, we assessed possible over- or under correction for tracer extravasation in two patients receiving contrast agent preloading and two patients not receiving preloading. Perfusion metrics for N = 60 patients diagnosed with either grade III (N = 14) or grade IV gliomas (N = 46) were analyzed across tissue types to evaluate the ability to distinguish regions with different hemodynamic patterns. Finally, N = 4 patient cases undergoing anti-angiogenic treatment are evaluated qualitatively for treatment effects. All patient data were acquired at 3.0 Tesla. RESULTS: The simulation studies showed good robustness against low signal-to-noise ratios, exemplified with Pearson correlations of R = 0.833 (mean transit time) and R = 0.738 (CTH) at signal-to-noise ratio = 20. Region-of-interest analysis of the N = 60 glioma patients showed that cerebral blood volume (CBV) significantly separated enhancing core from edema (grade IV: P < 10-8 , grade III: P < 0.05) and enhancing core from normal appearing ipsilateral white matter (NAWM) (grade IV: P < 10-8 , grade III: P < 0.05). The microvascular parameters were particularly good in separating edematous tissue from NAWM tissue in grade IV gliomas (P < 0.001). Finally, CTH separated grade III and grade IV core tissue (P < 0.05). CONCLUSION: We have demonstrated robustness of the proposed Bayesian algorithm against experimental noise and demonstrated complementary value in microvascular parameters to the CBV parameter in separating tissue types in gliomas. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:537-549.

Deployment and Adverse Pregnancy Outcomes: Primary Findings and Methodological Considerations.

Objective To characterize the pregnancy outcomes of women Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans including prevalence of preterm delivery, low birth weight, and macrosomia, and to highlight methodological limitations that can impact findings. Methods A retrospective cohort study was conducted starting in 2014 analyzing data from the 2009 to 2011 National Health Study for a New Generation of US Veterans, which sampled Veterans deployed and not deployed to OIF/OEF. All pregnancies resulting in a live birth were included, and categorized as occurring among non-deployers, before deployment, during deployment, or after deployment. Outcomes included preterm birth, low birth weight, and macrosomia. The association of deployment with selected outcomes was estimated using separate general estimating equations to account for lack of outcome independence among women contributing multiple pregnancies. Adjustment variables included maternal age at outcome, and race/ethnicity. Results There were 2276 live births (191 preterm births, 153 low birth weight infants, and 272 macrosomic infants). Compared with pregnancies before deployment, pregnancies among non-deployers and those after deployment appeared to have greater risk of preterm birth [non-deployers: odds ratio (OR) = 2.16, 95 % confidence interval (CI) 1.25, 3.72; after deployment: OR = 1.90, 95 % CI 0.90, 4.02]. A similar pattern was observed for low birth weight. No association of deployment with macrosomia was detected. Discussion Compared with non-deployers, those who eventually deploy appear to have better pregnancy outcomes prior to deployment, but this advantage is no longer apparent after deployment. Non-deployers may not be an appropriate reference group to study the putative health impacts of deployment on pregnancy outcomes.

White matter abnormalities are associated with chronic postconcussion symptoms in blast-related mild traumatic brain injury.

Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are nonspecific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of comorbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans were assigned to one of three groups including a blast-exposed no--TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI--LOC), and a blast-related mTBI with LOC group (mTBI + LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI + LOC group had more spatially heterogeneous white matter abnormalities than those in the no--TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI + LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS.