Cerebral blood flow territory instability in patients with atherosclerotic intracranial stenosis.

BACKGROUND: Stroke risk stratification in patients with symptomatic intracranial atherosclerotic arterial disease (ICAD) remains an important clinical objective owing to the high 14-19% recurrent stroke rate in these patients on standard-of-care medical management. There thus remains a need for hemodynamic markers that may allow for the selection of personalized therapies for high-risk symptomatic patients. PURPOSE: To determine if shifting of cerebral blood flow (CBF) territories in response to changes in cerebral perfusion pressure (CPP) may provide a marker for stroke risk in ICAD patients. STUDY TYPE: Prospective. POPULATION: Twenty ICAD patients who experienced a stroke within 45 days of study enrollment and 10 healthy controls. SEQUENCE: 3.0T MRI including anatomical imaging (T1 -weighted, T2 -weighted/FLAIR), 3D MR angiography, and normocapnic and hypercapnic vessel-encoded CBF-weighted arterial spin labeling. ASSESSMENT: Patients were scanned within 45 days of overt stroke and monitored (duration = 13.2 ± 4.4 months) for the endpoint of non-cardioembolic stroke or transient ischemic attack. Flow territory shifting (shifting index) was calculated from the first scan by determining whether a voxel shifted from its primary arterial source from normocapnia to hypercapnia. STATISTICAL TESTS: A Mann-Whitney U-test (significance: P < 0.05) was performed to determine whether patients meeting the endpoint had greater shifting indices relative to controls or patients not meeting the endpoint. RESULTS: Shifting indices (mean ± standard error) were significantly higher in patients meeting endpoint criteria relative to controls (P = 0.0057; adjusted P = 0.036) and patients not meeting endpoint criteria (P = 0.0047; adjusted P = 0.036). DATA CONCLUSION: Flow territory shifting may provide a marker of recurrent stroke risk in symptomatic ICAD patients on standard-of-care medical management therapies. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;50:1441-1451.

Machine learning analyses can differentiate meningioma grade by features on magnetic resonance imaging.

OBJECTIVEPrognostication and surgical planning for WHO grade I versus grade II meningioma requires thoughtful decision-making based on radiographic evidence, among other factors. Although conventional statistical models such as logistic regression are useful, machine learning (ML) algorithms are often more predictive, have higher discriminative ability, and can learn from new data. The authors used conventional statistical models and an array of ML algorithms to predict atypical meningioma based on radiologist-interpreted preoperative MRI findings. The goal of this study was to compare the performance of ML algorithms to standard statistical methods when predicting meningioma grade.METHODSThe cohort included patients aged 18-65 years with WHO grade I (n = 94) and II (n = 34) meningioma in whom preoperative MRI was obtained between 1998 and 2010. A board-certified neuroradiologist, blinded to histological grade, interpreted all MR images for tumor volume, degree of peritumoral edema, presence of necrosis, tumor location, presence of a draining vein, and patient sex. The authors trained and validated several binary classifiers: k-nearest neighbors models, support vector machines, naïve Bayes classifiers, and artificial neural networks as well as logistic regression models to predict tumor grade. The area under the curve-receiver operating characteristic curve was used for comparison across and within model classes. All analyses were performed in MATLAB using a MacBook Pro.RESULTSThe authors included 6 preoperative imaging and demographic variables: tumor volume, degree of peritumoral edema, presence of necrosis, tumor location, patient sex, and presence of a draining vein to construct the models. The artificial neural networks outperformed all other ML models across the true-positive versus false-positive (receiver operating characteristic) space (area under curve = 0.8895).CONCLUSIONSML algorithms are powerful computational tools that can predict meningioma grade with great accuracy.

Impact of vessel wall lesions and vascular stenoses on cerebrovascular reactivity in patients with intracranial stenotic disease.

PURPOSE: To compare cerebrovascular reactivity (CVR) and CVR lagtimes in flow territories perfused by vessels with vs. without proximal arterial wall disease and/or stenosis, separately in patients with atherosclerotic and nonatherosclerotic (moyamoya) intracranial stenosis. MATERIALS AND METHODS: Atherosclerotic and moyamoya patients with >50% intracranial stenosis and <70% cervical stenosis underwent angiography, vessel wall imaging (VWI), and CVR-weighted imaging (n = 36; vessel segments evaluated = 396). Angiography and VWI were evaluated for stenosis locations and vessel wall lesions. Maximum CVR and CVR lagtime were contrasted between vascular territories with and without proximal intracranial vessel wall lesions and stenosis, and a Wilcoxon rank-sum was test used to determine differences (criteria: corrected two-sided P < 0.05). RESULTS: CVR lagtime was prolonged in territories with vs. without a proximal vessel wall lesion or stenosis for both patient groups: moyamoya (CVR lagtime = 45.5 sec ± 14.2 sec vs. 35.7 sec ± 9.7 sec, P < 0.001) and atherosclerosis (CVR lagtime = 38.2 sec ± 9.1 sec vs. 35.0 sec ± 7.2 sec, P = 0.001). For reactivity, a significant decrease in maximum CVR in the moyamoya group only (maximum CVR = 9.8 ± 2.2 vs. 12.0 ± 2.4, P < 0.001) was observed. CONCLUSION: Arterial vessel wall lesions detected on noninvasive, noncontrast intracranial VWI in patients with intracranial stenosis correlate on average with tissue-level impairment on CVR-weighted imaging. LEVEL OF EVIDENCE: 4 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1167-1176.

Non-invasive imaging of oxygen extraction fraction in adults with sickle cell anaemia.

Sickle cell anaemia is a monogenetic disorder with a high incidence of stroke. While stroke screening procedures exist for children with sickle cell anaemia, no accepted screening procedures exist for assessing stroke risk in adults. The purpose of this study is to use novel magnetic resonance imaging methods to evaluate physiological relationships between oxygen extraction fraction, cerebral blood flow, and clinical markers of cerebrovascular impairment in adults with sickle cell anaemia. The specific goal is to determine to what extent elevated oxygen extraction fraction may be uniquely present in patients with higher levels of clinical impairment and therefore may represent a candidate biomarker of stroke risk. Neurological evaluation, structural imaging, and the non-invasive T2-relaxation-under-spin-tagging magnetic resonance imaging method were applied in sickle cell anaemia (n = 34) and healthy race-matched control (n = 11) volunteers without sickle cell trait to assess whole-brain oxygen extraction fraction, cerebral blood flow, degree of vasculopathy, severity of anaemia, and presence of prior infarct; findings were interpreted in the context of physiological models. Cerebral blood flow and oxygen extraction fraction were elevated (P < 0.05) in participants with sickle cell anaemia (n = 27) not receiving monthly blood transfusions (interquartile range cerebral blood flow = 46.2-56.8 ml/100 g/min; oxygen extraction fraction = 0.39-0.50) relative to controls (interquartile range cerebral blood flow = 40.8-46.3 ml/100 g/min; oxygen extraction fraction = 0.33-0.38). Oxygen extraction fraction (P < 0.0001) but not cerebral blood flow was increased in participants with higher levels of clinical impairment. These data provide support for T2-relaxation-under-spin-tagging being able to quickly and non-invasively detect elevated oxygen extraction fraction in individuals with sickle cell anaemia with higher levels of clinical impairment. Our results support the premise that magnetic resonance imaging-based assessment of elevated oxygen extraction fraction might be a viable screening tool for evaluating stroke risk in adults with sickle cell anaemia.

Assessment of lymphatic impairment and interstitial protein accumulation in patients with breast cancer treatment-related lymphedema using CEST MRI.

PURPOSE: Lymphatic impairment is known to reduce quality of life in some of the most crippling diseases of the 21st century, including obesity, lymphedema, and cancer. However, the lymphatics are not nearly as well-understood as other bodily systems, largely owing to a lack of sensitive imaging technologies that can be applied using standard clinical equipment. Here, proton exchange-weighted MRI is translated to the lymphatics in patients with breast cancer treatment-related lymphedema (BCRL). METHODS: Healthy volunteers (N = 8) and BCRL patients (N = 7) were scanned at 3 Tesla using customized structural MRI and amide proton transfer (APT) chemical exchange saturation transfer (CEST) MRI in sequence with the hypothesis that APT effects would be elevated in lymphedematous tissue. APT contrast, lymphedema stage, symptomatology, and histology information were evaluated. RESULTS: No significant difference between proton-weighted APT contrast in the right and left arms of healthy controls was observed. An increase in APT contrast in the affected arms of patients was found (P = 0.025; Cohen's d = 2.4), and variability among patients was consistent with documented damage to lymphatics as quantified by lymphedema stage. CONCLUSION: APT CEST MRI may have relevance for evaluating lymphatic impairment in patients with BCRL, and may extend to other pathologies where lymphatic compromise is evident.

Dual echo vessel-encoded ASL for simultaneous BOLD and CBF reactivity assessment in patients with ischemic cerebrovascular disease.

PURPOSE: Blood oxygenation level-dependent (BOLD)-weighted and vessel-encoded arterial spin labeling (VE-ASL) MRI provide complementary information and can be used in sequence to gauge hemodynamic contributions to cerebrovascular reactivity. Here, cerebrovascular reactivity is assessed using dual echo VE-ASL MRI to understand how VE labeling preparations influence BOLD and ASL contrast in flow-limited and healthy perfusion territories. METHODS: Patients (n = 12; age = 55 +/- 14 years; 6F/6M) presenting with ischemic steno-occlusive cerebrovascular disease underwent 3.0T angiographic imaging, T1 -weighted structural, and planning-free dual echo hypercarbic hyperoxic (i.e., carbogen) VE-ASL MRI. Vasculopathy extent, timecourses, and cerebrovascular reactivity (signal change and Z-statistic) for different VE-ASL images were contrasted across flow territories and Bonferroni-corrected P-values reported. RESULTS: BOLD cerebrovascular reactivity (i.e., long-TE VE-ASL) Z-statistics were similarly sensitive to asymmetric disease (P ≤ 0.002) regardless of labeling scenario. Cerebral blood flow reactivity correlated significantly with BOLD reactivity (Z-statistic). However, BOLD signal changes did not differ significantly between labeling scenarios (P > 0.003) or across territories (P > 0.002), indicating BOLD signal changes in response to carbogen offer low sensitivity to lateralizing disease. CONCLUSION: Dual echo VE-ASL can provide simultaneous cerebral blood flow and qualitative BOLD contrast consistent with lateralizing disease severity in patients with asymmetric steno-occlusive disease. The methodological strengths and limitations of composite BOLD and VE-ASL measurements in the clinic are discussed.

In vivo quantification of hyperoxic arterial blood water T1.

Normocapnic hyperoxic and hypercapnic hyperoxic gas challenges are increasingly being used in cerebrovascular reactivity (CVR) and calibrated functional MRI experiments. The longitudinal arterial blood water relaxation time (T1a) change with hyperoxia will influence signal quantification through mechanisms relating to elevated partial pressure of plasma-dissolved O2 (pO2) and increased oxygen bound to hemoglobin in arteries (Ya) and veins (Yv). The dependence of T1a on Ya and Yv has been elegantly characterized ex vivo; however, the combined influence of pO2, Ya and Yv on T1a in vivo under normal ventilation has not been reported. Here, T1a is calculated during hyperoxia in vivo by a heuristic approach that evaluates T1 -dependent arterial spin labeling (ASL) signal changes to varying gas stimuli. Healthy volunteers (n = 14; age, 31.5 ± 7.2 years) were scanned using pseudo-continuous ASL in combination with room air (RA; 21% O2/79% N2), hypercapnic normoxic (HN; 5% CO2/21% O2/74% N2) and hypercapnic hyperoxic (HH; 5% CO2/95% O2) gas administration. HH T1a was calculated by requiring that the HN and HH cerebral blood flow (CBF) change be identical. The HH protocol was then repeated in patients (n = 10; age, 61.4 ± 13.3 years) with intracranial stenosis to assess whether an HH T1a decrease prohibited ASL from being performed in subjects with known delayed blood arrival times. Arterial blood T1a decreased from 1.65 s at baseline to 1.49 ± 0.07 s during HH. In patients, CBF values in the affected flow territory for the HH condition were increased relative to baseline CBF values and were within the physiological range (RA CBF = 36.6 ± 8.2 mL/100 g/min; HH CBF = 45.2 ± 13.9 mL/100 g/min). It can be concluded that hyperoxic (95% O2) 3-T arterial blood T1aHH = 1.49 ± 0.07 s relative to a normoxic T1a of 1.65 s.

Routine clinical evaluation of cerebrovascular reserve capacity using carbogen in patients with intracranial stenosis.

BACKGROUND AND PURPOSE: A promising method for identifying hemodynamic impairment that may serve as a biomarker for stroke risk in patients with intracranial stenosis is cerebrovascular reactivity (CVR) mapping using noninvasive MRI. Here, abilities to measure CVR safely in the clinic using hypercarbic hyperoxic (carbogen) gas challenges, which increase oxygen delivery to tissue, are investigated. METHODS: In sequence with structural and angiographic imaging, blood oxygenation level-dependent carbogen-induced CVR scans were performed in patients with symptomatic intracranial stenosis (n=92) and control (n=10) volunteers, with a subgroup of patients (n=57) undergoing cerebral blood flow-weighted pseudocontinuous arterial spin labeling CVR. Subjects were stratified for 4 substudies to evaluate relationships between (1) carbogen and hypercarbic normoxic CVR in healthy tissue (n=10), (2) carbogen cerebral blood flow CVR and blood oxygenation level-dependent CVR in intracranial stenosis patients (n=57), (3) carbogen CVR and clinical measures of disease in patients with asymmetrical intracranial atherosclerotic (n=31) and moyamoya (n=29) disease, and (4) the CVR scan and immediate and longer-term complications (n=92). RESULTS: Noninvasive blood oxygenation level-dependent carbogen-induced CVR values correlate with (1) lobar hypercarbic normoxic gas stimuli in healthy tissue (R=0.92; P<0.001), (2) carbogen-induced cerebral blood flow CVR in patients with intracranial stenosis (R=0.30-0.33; P<0.012), and (3) angiographic measures of disease severity both in atherosclerotic and moyamoya patients after appropriate processing. No immediate stroke-related complications were reported in response to carbogen administration; longer-term neurological events fell within the range for expected events in this patient population. CONCLUSIONS: Carbogen-induced CVR elicited no added adverse events and provided a surrogate marker of cerebrovascular reserve consistent with intracranial vasculopathy.

Assessment of ischemic penumbra in patients with hyperacute stroke using amide proton transfer (APT) chemical exchange saturation transfer (CEST) MRI.

Chemical exchange saturation transfer (CEST)-derived, pH-weighted, amide proton transfer (APT) MRI has shown promise in animal studies for the prediction of infarction risk in ischemic tissue. Here, APT MRI was translated to patients with acute stroke (1-24 h post-symptom onset), and assessments of APT contrast, perfusion, diffusion, disability and final infarct volume (23-92 days post-stroke) are reported. Healthy volunteers (n = 5) and patients (n = 10) with acute onset of symptoms (0-4 h, n = 7; uncertain onset <24 h, n = 3) were scanned with diffusion- and perfusion-weighted MRI, fluid-attenuated inversion recovery (FLAIR) and CEST. Traditional asymmetry and a Lorentzian-based APT index were calculated in the infarct core, at-risk tissue (time-to-peak, TTP; lengthening) and final infarct volume. On average (mean ± standard deviation), control white matter APT values (asymmetry, 0.019 ± 0.005; Lorentzian, 0.045 ± 0.006) were not significantly different (p > 0.05) from APT values in normal-appearing white matter (NAWM) of patients (asymmetry, 0.022 ± 0.003; Lorentzian, 0.048 ± 0.003); however, ischemic regions in patients showed reduced (p = 0.03) APT effects compared with NAWM. Representative cases are presented, whereby the APT contrast is compared quantitatively with contrast from other imaging modalities. The findings vary between patients; in some patients, a trend for a reduction in the APT signal in the final infarct region compared with at-risk tissue was observed, consistent with tissue acidosis. However, in other patients, no relationship was observed in the infarct core and final infarct volume. Larger clinical studies, in combination with focused efforts on sequence development at clinically available field strengths (e.g. 3.0 T), are necessary to fully understand the potential of APT imaging for guiding the hyperacute management of patients.

Reduction in the number and associated costs of unindicated dual-phase head CT examinations after a quality improvement initiative.

OBJECTIVE: During this study, we instituted a phased quality improvement initiative designed to educate referring clinicians and departmental radiologists about the recommendations of the American College of Radiology (ACR) Appropriateness Criteria for dual-phase (without and with contrast material) head CT examinations. The primary aims of the study were to evaluate whether the quality improvement initiative was associated with an improvement in ACR Appropriateness Criteria appropriateness ratings and a reduction in the number of unindicated dual-phase head CT examinations performed. A secondary aim was to assess the impact of the quality improvement initiative on health care costs. MATERIALS AND METHODS: This study included-with the exception of the examinations performed during a 3-month training period-all single- and dual-phase head CT examinations performed of adult patients at a tertiary care medical center from January 2009 through October 2011. Both inpatients and outpatient examinations were included. There were no exclusion criteria. RESULTS: Implementation of the initiative enhanced patient safety and reduced health care costs by achieving a significant reduction (p = 0.006) in the number of unindicated dual-phase head CT examinations performed from a median number of 40 per month to 17 per month. CONCLUSION: Although there are potential benefits for dual-phase head CT examinations, the medical and economic risks should be measured against these potential benefits. Incorporating the ACR Appropriateness Criteria applies evidence-based medicine to this algorithm. In this outcomes-driven study, the number of unindicated dual-phase head CT examinations was reduced and imaging efficacy improved primarily through physician education and monitoring.

Novel MRI approaches for assessing cerebral hemodynamics in ischemic cerebrovascular disease.

Changes in cerebral hemodynamics underlie a broad spectrum of ischemic cerebrovascular disorders. An ability to accurately and quantitatively measure hemodynamic (cerebral blood flow and cerebral blood volume) and related metabolic (cerebral metabolic rate of oxygen) parameters is important for understanding healthy brain function and comparative dysfunction in ischemia. Although positron emission tomography, single-photon emission tomography, and gadolinium-MRI approaches are common, more recently MRI approaches that do not require exogenous contrast have been introduced with variable sensitivity for hemodynamic parameters. The ability to obtain hemodynamic measurements with these new approaches is particularly appealing in clinical and research scenarios in which follow-up and longitudinal studies are necessary. The purpose of this review is to outline current state-of-the-art MRI methods for measuring cerebral blood flow, cerebral blood volume, and cerebral metabolic rate of oxygen and provide practical tips to avoid imaging pitfalls. MRI studies of cerebrovascular disease performed without exogenous contrast are synopsized in the context of clinical relevance and methodological strengths and limitations.

CT virtual endoscopy in the evaluation of large airway disease: review.

OBJECTIVE: The purpose of this article is to illustrate the usefulness and limitations of CT virtual endoscopy in the evaluation of large airway disease. CONCLUSION: CT virtual endoscopy is a postprocessing tool that is easy to perform and that can aid in depicting disorders of the large airways without additional radiation or cost other than added time in postprocessing. The benefits of this technique include noninvasive diagnostic surveillance and preoperative planning.

Differentiating meningioma grade by imaging features on magnetic resonance imaging.

Atypical meningioma has an aggressive clinical course. Distinguishing atypical from benign meningioma preoperatively could affect surgical planning and improve treatment outcomes. In this study, we examined whether pre-operative magnetic resonance imaging (MRI) features could distinguish between benign and atypical meningioma. Imaging factors analyzed included peritumoral edema, the presence of a draining vein, tumor necrosis, tumor location and tumor volume. Using univariate analysis, the most striking predictor of grade was tumor volume (p < .001). When adjusting for the degree of peritumoral edema, volume remained a positive predictor of higher histological grade meningioma (p = .042) and was the strongest single predictor of higher-grade meningioma in this study. Additional imaging features associated with increased risk for atypical pathology in univariate analysis included the presence of tumor necrosis (p = .012), peritumoral edema (p = .022) and location along the falx and convexity (p = .026). Despite statistically significant associations using univariate analysis, in multivariate analysis, we found that only presence of peritumoral edema was predictive of a higher-grade meningioma. Further multivariate analyses suggests that edema, draining vein and necrosis are all positive predictors of tumor volume (p < .0001). Overall, these data suggest that radiographic features including presence of tumor necrosis, and tumor location along the falx or convexity may be predictive of higher-grade meningioma when considered alone. However, most strikingly, our data point to tumor volume as the most robust pre-operative indicator of higher-grade meningioma.

Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD): a scoring system for moyamoya severity based on multimodal hemodynamic imaging.

OBJECTIVE Quantification of the severity of vasculopathy and its impact on parenchymal hemodynamics is a necessary prerequisite for informing management decisions and evaluating intervention response in patients with moyamoya. The authors performed digital subtraction angiography and noninvasive structural and hemodynamic MRI, and they outline a new classification system for patients with moyamoya that they have named Prior Infarcts, Reactivity, and Angiography in Moyamoya Disease (PIRAMD). METHODS Healthy control volunteers (n = 11; age 46 ± 12 years [mean ± SD]) and patients (n = 25; 42 ± 13.5 years) with angiographically confirmed moyamoya provided informed consent and underwent structural (T1-weighted, T2-weighted, FLAIR, MR angiography) and hemodynamic (T2*- and cerebral blood flow-weighted) 3-T MRI. Cerebrovascular reactivity (CVR) in the internal carotid artery territory was assessed using susceptibility-weighted MRI during a hypercapnic stimulus. Only hemispheres without prior revascularization were assessed. Each hemisphere was considered symptomatic if localizing signs were present on neurological examination and/or there was a history of transient ischemic attack with symptoms referable to that hemisphere. The PIRAMD factor weighting versus symptomatology was optimized using binary logistic regression and receiver operating characteristic curve analysis with bootstrapping. The PIRAMD finding was scored from 0 to 10. For each hemisphere, 1 point was assigned for prior infarct, 3 points for reduced CVR, 3 points for a modified Suzuki Score ≥ Grade II, and 3 points for flow impairment in ≥ 2 of 7 predefined vascular territories. Hemispheres were divided into 3 severity grades based on total PIRAMD score, as follows: Grade 1, 0-5 points; Grade 2, 6-9 points; and Grade 3, 10 points. RESULTS In 28 of 46 (60.9%) hemispheres the findings met clinical symptomatic criteria. With decreased CVR, the odds ratio of having a symptomatic hemisphere was 13 (95% CI 1.1-22.6, p = 0.002). The area under the curve for individual PIRAMD factors was 0.67-0.72, and for the PIRAMD grade it was 0.845. There were 0/8 (0%), 10/18 (55.6%), and 18/20 (90%) symptomatic PIRAMD Grade 1, 2, and 3 hemispheres, respectively. CONCLUSIONS A scoring system for total impairment is proposed that uses noninvasive MRI parameters. This scoring system correlates with symptomatology and may provide a measure of hemodynamic severity in moyamoya, which could be used for guiding management decisions and evaluating intervention response.

Planning-free cerebral blood flow territory mapping in patients with intracranial arterial stenosis.

A noninvasive method for quantifying cerebral blood flow and simultaneously visualizing cerebral blood flow territories is vessel-encoded pseudocontinuous arterial spin labeling MRI. However, obstacles to acquiring such information include limited access to the methodology in clinical centers and limited work on how clinically acquired vessel-encoded pseudocontinuous arterial spin labeling data correlate with gold-standard methods. The purpose of this work is to develop and validate a semiautomated pipeline for the online quantification of cerebral blood flow maps and cerebral blood flow territories from planning-free vessel-encoded pseudocontinuous arterial spin labeling MRI with gold-standard digital subtraction angiography. Healthy controls (n = 10) and intracranial atherosclerotic disease patients (n = 34) underwent 3.0 T MRI imaging including vascular (MR angiography) and hemodynamic (cerebral blood flow-weighted arterial spin labeling) MRI. Patients additionally underwent catheter and/or CT angiography. Variations in cross-territorial filling were grouped according to diameters of circle of Willis vessels in controls. In patients, Cohen's k-statistics were computed to quantify agreement in perfusion patterns between vessel-encoded pseudocontinuous arterial spin labeling and angiography. Cross-territorial filling patterns were consistent with circle of Willis anatomy. The intraobserver Cohen's k-statistics for cerebral blood flow territory and digital subtraction angiography perfusion agreement were 0.730 (95% CI = 0.593-0.867; reader one) and 0.708 (95% CI = 0.561-0.855; reader two). These results support the feasibility of a semiautomated pipeline for evaluating major neurovascular cerebral blood flow territories in patients with intracranial atherosclerotic disease.

Time delay processing of hypercapnic fMRI allows quantitative parameterization of cerebrovascular reactivity and blood flow delays.

Blood oxygenation level-dependent fMRI contrast depends on the volume and oxygenation of blood flowing through the circulatory system. The effects on image intensity depend temporally on the arrival of blood within a voxel, and signal can be monitored during the time course of such blood flow. It has been previously shown that the passage of global endogenous variations in blood volume and oxygenation can be tracked as blood passes through the brain by determining the strength and peak time lag of their cross-correlation with blood oxygenation level-dependent data. By manipulating blood composition using transient hypercarbia and hyperoxia, we can induce much larger oxygenation and volume changes in the blood oxygenation level-dependent signal than result from natural endogenous fluctuations. This technique was used to examine cerebrovascular parameters in healthy subjects (n = 8) and subjects with intracranial stenosis (n = 22), with a subgroup of intracranial stenosis subjects scanned before and after surgical revascularization (n = 6). The halfwidth of cross-correlation lag times in the brain was larger in IC stenosis subjects (21.21 ± 14.22 s) than in healthy control subjects (8.03 ± 3.67), p < 0.001, and was subsequently reduced in regions that co-localized with surgical revascularization. These data show that blood circulatory timing can be measured robustly and longitudinally throughout the brain using simple respiratory challenges.

Crossed cerebellar diaschisis after stroke identified noninvasively with cerebral blood flow-weighted arterial spin labeling MRI.

BACKGROUND AND PURPOSE: Crossed cerebellar diaschisis (CCD) is most commonly investigated using hemodynamic PET and SPECT imaging. However, noninvasive MRI offers advantages of improved spatial resolution, allowing hemodynamic changes to be compared directly with structural findings and without concerns related to ionizing radiation exposure. The aim of this study was to evaluate relationships between CCD identified from cerebral blood flow (CBF)-weighted arterial spin labeling (ASL) MRI with cerebrovascular reactivity (CVR)-weighted blood oxygenation level dependent (BOLD) MRI, Wallerian degeneration, clinical motor impairment, and corticospinal tract involvement. METHODS: Subjects (n=74) enrolled in an ongoing observational stroke trial underwent CBF-weighted ASL and hypercapnic CVR-weighted BOLD MRI. Hemispheric asymmetry indices for basal cerebellar CBF, cerebellar CVR, and cerebral peduncular area were compared between subjects with unilateral supratentorial infarcts (n=18) and control subjects without infarcts (n=16). CCD required (1) supratentorial infarct and (2) asymmetric cerebellar CBF (>95% confidence interval relative to controls). RESULTS: In CCD subjects (n=9), CVR (p=0.04) and cerebral peduncular area (p<0.01) were significantly asymmetric compared to controls. Compared to infarct subjects not meeting CCD criteria (n=9), CCD subjects had no difference in corticospinal tract location for infarct (p=1.0) or motor impairment (p=0.08). CONCLUSIONS: CCD correlated with cerebellar CVR asymmetry and Wallerian degeneration. These findings suggest that noninvasive MRI may be a useful alternative to PET or SPECT to study structural correlates and clinical consequences of CCD following supratentorial stroke.

Alterations in default-mode network connectivity may be influenced by cerebrovascular changes within 1 week of sports related concussion in college varsity athletes: a pilot study.

The goal of this pilot study is to use complementary MRI strategies to quantify and relate cerebrovascular reactivity, resting cerebral blood flow and functional connectivity alterations in the first week following sports concussion in college varsity athletes. Seven college athletes (3F/4M, age = 19.7 ± 1.2 years) were imaged 3-6 days following a diagnosed sports related concussion and compared to eleven healthy controls with no history of concussion (5M/6F, 18-23 years, 7 athletes). Cerebrovascular reactivity and functional connectivity were measured using functional MRI during a hypercapnia challenge and via resting-state regional partial correlations, respectively. Resting cerebral blood flow was quantified using arterial spin labeling MRI methods. Group comparisons were made within and between 18 regions of interest. Cerebrovascular reactivity was increased after concussion when averaged across all regions of interest (p = 0.04), and within some default-mode network regions, the anterior cingulate and the right thalamus (p < 0.05) independently. The FC was increased in the concussed athletes within the default-mode network including the left and right hippocampus, precuneus and ventromedial prefrontal cortex (p < 0.01), with measures being linearly related to cerebrovascular reactivity in the hippocampus in the concussed athletes. Significant resting cerebral blood flow changes were not detected between the two groups. This study provides evidence for increased cerebrovascular reactivity and functional connectivity in the medial regions of the default-mode network within days of a single sports related concussion in college athletes. Our findings emphasize the utility of complementary cerebrovascular measures in the interpretation of alterations in functional connectivity following concussion.

The cumulative influence of hyperoxia and hypercapnia on blood oxygenation and R*2.

Cerebrovascular reactivity (CVR)-weighted blood-oxygenation-level-dependent magnetic resonance imaging (BOLD-MRI) experiments are frequently used in conjunction with hyperoxia. Owing to complex interactions between hyperoxia and hypercapnia, quantitative effects of these gas mixtures on BOLD responses, blood and tissue R2*, and blood oxygenation are incompletely understood. Here we performed BOLD imaging (3 T; TE/TR=35/2,000 ms; spatial resolution=3 × 3 × 3.5 mm(3)) in healthy volunteers (n=12; age=29±4.1 years) breathing (i) room air (RA), (ii) normocapnic-hyperoxia (95% O2/5% N2, HO), (iii) hypercapnic-normoxia (5% CO2/21% O2/74% N2, HC-NO), and (iv) hypercapnic-hyperoxia (5% CO2/95% O2, HC-HO). For HC-HO, experiments were performed with separate RA and HO baselines to control for changes in O2. T2-relaxation-under-spin-tagging MRI was used to calculate basal venous oxygenation. Signal changes were quantified and established hemodynamic models were applied to quantify vasoactive blood oxygenation, blood-water R2*, and tissue-water R2*. In the cortex, fractional BOLD changes (stimulus/baseline) were HO/RA=0.011±0.007; HC-NO/RA=0.014±0.004; HC-HO/HO=0.020±0.008; and HC-HO/RA=0.035±0.010; for the measured basal venous oxygenation level of 0.632, this led to venous blood oxygenation levels of 0.660 (HO), 0.665 (HC-NO), and 0.712 (HC-HO). Interleaving a HC-HO stimulus with HO baseline provided a smaller but significantly elevated BOLD response compared with a HC-NO stimulus. Results provide an outline for how blood oxygenation differs for several gas stimuli and provides quantitative information on how hypercapnic BOLD CVR and R2* are altered during hyperoxia.

Correlating hemodynamic magnetic resonance imaging with high-field intracranial vessel wall imaging in stroke.

Vessel wall magnetic resonance imaging at ultra-high field (7 Tesla) can be used to visualize vascular lesions noninvasively and holds potential for improving stroke-risk assessment in patients with ischemic cerebrovascular disease. We present the first multi-modal comparison of such high-field vessel wall imaging with more conventional (i) 3 Tesla hemodynamic magnetic resonance imaging and (ii) digital subtraction angiography in a 69-year-old male with a left temporal ischemic infarct.