Megan K. Strother

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.

Relationships between hypercarbic reactivity, cerebral blood flow, and arterial circulation times in patients with moyamoya disease

To evaluate the correlation between angiographic measures of Moyamoya disease and tissue‐level impairment from measurements of tissue perfusion and cerebrovascular reactivity (CVR).

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.

Bolus arrival time and cerebral blood flow responses to hypercarbia

The purpose of this study was to evaluate how cerebral blood flow and bolus arrival time (BAT) measures derived from arterial spin labeling (ASL) MRI data change for different hypercarbic gas stimuli. Pseudocontinuous ASL (pCASL) was applied (3.0T; spatial resolution = 4 × 4 × 7 mm 3 ; repetition time/echo time (TR/TE) = 3,600/11 ms) sequentially in healthy volunteers (n = 12; age = 30±4 years) for separate experiments in which (i) normocarbic normoxia (i.e., room air), hypercarbic normoxia (i.e., 5% CO2/21% O2/74% N2), and hypercarbic hyperoxia (i.e., carbogen: 5% CO2/95% O2) gas was administered (12 L/minute). Cerebral blood flow and BAT changes were quantified using models that account for macrovascular signal and partial volume effects in all gray matter and regionally in cerebellar, temporal, occipital, frontal, and parietal lobes. Regional reductions in BAT of 4.6% to 7.7% and 3.3% to 6.6% were found in response to hypercarbic normoxia and hypercarbic hyperoxia, respectively. Cerebral blood flow increased by 8.2% to 27.8% and 3.5% to 19.8% for hypercarbic normoxia and hypercarbic hyperoxia, respectively. These findings indicate that changes in BAT values may bias functional ASL data and thus should be considered when choosing appropriate experimental parameters in calibrated functional magnetic resonance imaging or ASL cerebrovascular reactivity experiments that use hypercarbic gas stimuli.

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.

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

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.

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.

The vascular steal phenomenon is an incomplete contributor to negative cerebrovascular reactivity in patients with symptomatic intracranial stenosis.

‘Vascular steal’ has been proposed as a compensatory mechanism in hemodynamically compromised ischemic parenchyma. Here, independent measures of cerebral blood flow (CBF) and blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) responses to a vascular stimulus in patients with ischemic cerebrovascular disease are recorded. Symptomatic intracranial stenosis patients (n = 40) underwent a multimodal 3.0T MRI protocol including structural (T1-weighted and T2-weighted fluid-attenuated inversion recovery) and hemodynamic (BOLD and CBF-weighted arterial spin labeling) functional MRI during room air and hypercarbic gas administration. CBF changes in regions demonstrating negative BOLD reactivity were recorded, as well as clinical correlates including symptomatic hemisphere by infarct and lateralizing symptoms. Fifteen out of forty participants exhibited negative BOLD reactivity. Of these, a positive relationship was found between BOLD and CBF reactivity in unaffected (stenosis degree <50%) cortex. In negative BOLD cerebrovascular reactivity regions, three patients exhibited significant (P < 0.01) reductions in CBF consistent with vascular steal; six exhibited increases in CBF; and the remaining exhibited no statistical change in CBF. Secondary findings were that negative BOLD reactivity correlated with symptomatic hemisphere by lateralizing clinical symptoms and prior infarcts(s). These data support the conclusion that negative hypercarbia-induced BOLD responses, frequently assigned to vascular steal, are heterogeneous in origin with possible contributions from autoregulation and/or metabolism.

Cerebrovascular Collaterals Correlate with Disease Severity in Adult North American Patients with Moyamoya Disease

BACKGROUND AND PURPOSE: Cerebrovascular collaterals have been increasingly recognized as predictive of clinical outcomes in Moyamoya disease in Asia. The aim of this study was to characterize collaterals in North American adult patients with Moyamoya disease and to assess whether similar correlations are valid. MATERIALS AND METHODS: Patients with Moyamoya disease (n = 39; mean age, 43.5 ±10.6 years) and age- and sex-matched control subjects (n = 33; mean age, 44.3 ± 12.0 years) were graded via angiography. Clinical symptoms of stroke or hemorrhage were graded separately by imaging. Correlations between collateralization and disease severity, measured by the modified Suzuki score, were evaluated in patients with Moyamoya disease by fitting a regression model with clustered ordinal multinomial responses. RESULTS: The presence of leptomeningeal collaterals (P = .008), dilation of the anterior choroidal artery (P = .01), and the posterior communicating artery/ICA ratio (P = .004) all correlated significantly with disease severity. The presence of infarct or hemorrhage and posterior steno-occlusive disease did not correlate significantly with the modified Suzuki score (P = .1). Anterior choroidal artery changes were not specific for hemorrhage. Patients with Moyamoya disease were statistically more likely than controls to have higher posterior communicating artery/ICA ratios and a greater incidence of leptomeningeal collaterals. CONCLUSIONS: As with Moyamoya disease in Asian patients, the presence of cerebrovascular collaterals correlated with the modified Suzuki score for disease severity in North American patients with Moyamoya disease. However, anterior choroidal artery changes, which correlated with increased rates of hemorrhage in Asian studies, were not specific to hemorrhage in North Americans.

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

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).