Allison O. Scott

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

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).

The Cumulative Influence of Hyperoxia and Hypercapnia on Blood Oxygenation and R2

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 (3T; TE/TR = 35/2,000 ms; spatial resolution = 3×3×3.5 mm3) 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 R∗2, and tissue-water R∗2. 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 R∗2 are altered during hyperoxia.

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 Cohens 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.

Interrogating the Functional Correlates of Collateralization in Patients with Intracranial Stenosis Using Multimodal Hemodynamic Imaging

The authors assessed correlations among baseline perfusion and arterial transit time artifacts, cerebrovascular reactivity, and the presence of collateral vessels on digital subtraction angiography. Arterial spin-labeling MRI and DSA were compared with BOLD MR imaging measures of hypercapnic cerebrovascular reactivity in 18 patients with symptomatic intracranial stenosis. In regions with normal-to-high signal on ASL, collateral vessel presence on DSA strongly correlated with declines in cerebrovascular reactivity (as measured on BOLD MRI). These data support the use of ASL MR imaging rather than invasive DSA to assess the presence of collateralization, even for patients with internal carotid stenosis from nonatherosclerotic etiologies. Also, collaterals identified on ASL with arterial transit artifacts correlated with decreased CVR compared with regions not perfused via collaterals. BACKGROUND AND PURPOSE: The importance of collateralization for maintaining adequate cerebral perfusion is increasingly recognized. However, measuring collateral flow noninvasively has proved elusive. The aim of this study was to assess correlations among baseline perfusion and arterial transit time artifacts, cerebrovascular reactivity, and the presence of collateral vessels on digital subtraction angiography. MATERIALS AND METHODS: The relationship between the presence of collateral vessels on arterial spin-labeling MR imaging and DSA was compared with blood oxygen level–dependent MR imaging measures of hypercapnic cerebrovascular reactivity in patients with symptomatic intracranial stenosis (n = 18). DSA maps were reviewed by a neuroradiologist and assigned the following scores: 1, collaterals to the periphery of the ischemic site; 2, complete irrigation of the ischemic bed via collateral flow; and 3, normal antegrade flow. Arterial spin-labeling maps were scored according to the following: 0, low signal; 1, moderate signal with arterial transit artifacts; 2, high signal with arterial transit artifacts; and 3, normal signal. RESULTS: In regions with normal-to-high signal on arterial spin-labeling, collateral vessel presence on DSA strongly correlated with declines in cerebrovascular reactivity (as measured on blood oxygen level–dependent MR imaging, P < .001), most notably in patients with nonatherosclerotic disease. There was a trend toward increasing cerebrovascular reactivity with increases in the degree of collateralization on DSA (P = .082). CONCLUSIONS: Collateral vessels may have fundamentally different vasoreactivity properties from healthy vessels, a finding that is observed most prominently in nonatherosclerotic disease and, to a lesser extent, in atherosclerotic disease.

Lymphedema evaluation using noninvasive 3T MR lymphangiography

To exploit the long 3.0T relaxation times and low flow velocity of lymphatic fluid to develop a noninvasive 3.0T lymphangiography sequence and evaluate its relevance in patients with lymphedema.

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

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.

Hemodynamic mechanisms underlying elevated oxygen extraction fraction (OEF) in moyamoya and sickle cell anemia patients

Moyamoya is a bilateral, complex cerebrovascular condition characterized by progressive non-atherosclerotic intracranial stenosis and collateral vessel formation. Moyamoya treatment focuses on restoring cerebral blood flow (CBF) through surgical revascularization, however stratifying patients for revascularization requires abilities to quantify how well parenchyma is compensating for arterial steno-occlusion. Globally elevated oxygen extraction fraction (OEF) secondary to CBF reduction may serve as a biomarker for tissue health in moyamoya patients, as suggested in patients with sickle cell anemia (SCA) and reduced oxygen carrying capacity. Here, OEF was measured (TRUST-MRI) to test the hypothesis that OEF is globally elevated in patients with moyamoya (n = 18) and SCA (n = 18) relative to age-matched controls (n = 43). Mechanisms underlying the hypothesized OEF increases were evaluated by performing sequential CBF-weighted, cerebrovascular reactivity (CVR)-weighted, and structural MRI. Patients were stratified by treatment and non-parametric tests applied to compare study variables (significance: two-sided P < 0.05). OEF was significantly elevated in moyamoya participants (interquartile range = 0.38–0.45) compared to controls (interquartile range = 0.29–0.38), similar to participants with SCA (interquartile range = 0.37–0.45). CBF was inversely correlated with OEF in moyamoya participants. Elevated OEF was only weakly related to reductions in CVR, consistent with basal CBF level, rather than vascular reserve capacity, being most closely associated with OEF.

3.0 T relaxation time measurements of human lymph nodes in adults with and without lymphatic insufficiency: Implications for magnetic resonance lymphatic imaging

The purpose of this work was to quantify 3.0 T (i) T1 and T2 relaxation times of in vivo human lymph nodes (LNs) and (ii) LN relaxometry differences between healthy LNs and LNs from patients with lymphatic insufficiency secondary to breast cancer treatment‐related lymphedema (BCRL). MR relaxometry was performed over bilateral axillary regions at 3.0 T in healthy female controls (105 LNs from 20 participants) and patients with BCRL (108 LNs from 20 participants). Quantitative T1 maps were calculated using a multi‐flip‐angle (20, 40, 60°) method with B1 correction (dual‐TR method, TR1/TR2 = 30/130 ms), and T2 maps using a multi‐echo (TE = 9–189 ms; 12 ms intervals) method. T1 and T2 were quantified in the LN cortex and hilum. A Mann–Whitney U‐test was applied to compare LN relaxometry values between patients and controls (significance, two sided, p < 0.05). Linear regression was applied to evaluate how LN relaxometry varied with age, BMI, and clinical indicators of disease. LN substructure relaxation times (mean ± standard deviation) in healthy controls were T1 cortex, 1435 ± 391 ms; T1 hilum, 714 ± 123 ms; T2 cortex, 102 ± 12 ms, and T2 hilum, 119 ± 21 ms. T1 of the LN cortex was significantly reduced in the contralateral axilla of BCRL patients compared with the axilla on the surgical side (p < 0.001) and compared with bilateral control values (p < 0.01). The LN cortex T1 asymmetry discriminated cases from controls (p = 0.004) in a multiple linear regression, accounting for age and BMI. Human 3.0 T T1 and T2 relaxation times in axillary LNs were quantified for the first time in vivo. Measured values are relevant for optimizing acquisition parameters in anatomical lymphatic imaging sequences, and can serve as a reference for novel functional and molecular LN imaging methods that require quantitative knowledge of LN relaxation times.