Clinical Feasibility of Noninvasive Visualization of Lymphatic Flow with Principles of Spin Labeling MR Imaging: Implications for Lymphedema Assessment

Purpose To extend a commonly used noninvasive arterial spin labeling magnetic resonance (MR) imaging method for measuring blood flow to evaluate lymphatic flow. Materials and Methods All volunteers (n = 12) provided informed consent in accordance with institutional review board and HIPAA regulations. Quantitative relaxation time (T1 and T2) measurements were made in extracted human lymphatic fluid at 3.0 T. Guided by these parameters, an arterial spin labeling MR imaging approach was adapted to measure lymphatic flow (flow-alternating inversion-recovery lymphatic water labeling, 3 × 3 × 5 mm) in healthy subjects (n = 6; mean age, 30 years ± 1 [standard deviation]; recruitment duration, 2 months). Lymphatic flow velocity was quantified by performing spin labeling measurements as a function of postlabeling delay time and by measuring time to peak signal intensity in axillary lymph nodes. Clinical feasibility was evaluated in patients with stage II lymphedema (three women; age range, 43–64 years) and in control subjects with unilateral cuff-induced lymphatic stenosis (one woman, two men; age range, 31–35 years). Results Mean T1 and T2 relaxation times of lymphatic fluid at 3.0 T were 3100 msec ± 160 (range, 2930–3210 msec; median, 3200 msec) and 610 msec ± 12 (range, 598–618 msec; median, 610 msec), respectively. Healthy lymphatic flow (afferent vessel to axillary node) velocity was 0.61 cm/min ± 0.13 (n = 6). A reduction (P \u3c .005) in lymphatic flow velocity in the affected arms of patients and the affected arms of healthy subjects with manipulated cuff-induced flow reduction was observed. The ratio of unaffected to affected axilla lymphatic velocity (1.24 ± 0.18) was significantly (P \u3c .005) higher than the left-to-right ratio in healthy subjects (0.91 ± 0.18). Conclusion This work provides a foundation for clinical investigations whereby lymphedema etiogenesis and therapies may be interrogated without exogenous agents and with clinically available imaging equipment

Hemodynamic and metabolic changes during hypercapnia with normoxia and hyperoxia using pCASL and TRUST MRI in healthy adults

Blood oxygenation level-dependent (BOLD) or arterial spin labeling (ASL) MRI with hypercapnic stimuli allow for measuring cerebrovascular reactivity (CVR). Hypercapnic stimuli are also employed in calibrated BOLD functional MRI for quantifying neuronally-evoked changes in cerebral oxygen metabolism (CMRO 2). It is often assumed that hypercapnic stimuli (with or without hyperoxia) are iso-metabolic; increasing arterial CO 2 or O 2 does not affect CMRO 2. We evaluated the null hypothesis that two common hypercapnic stimuli, 'CO 2 in air' and carbogen, are iso-metabolic. TRUST and ASL MRI were used to measure the cerebral venous oxygenation and cerebral blood flow (CBF), from which the oxygen extraction fraction (OEF) and CMRO 2 were calculated for room-air, 'CO 2 in air' and carbogen. As expected, CBF significantly increased (9.9% ± 9.3% and 12.1% ± 8.8% for 'CO 2 in air' and carbogen, respectively). CMRO 2 decreased for 'CO 2 in air' (-13.4% ± 13.0%, p < 0.01) compared to room-air, while the CMRO 2 during carbogen did not significantly change. Our findings indicate that 'CO 2 in air' is not iso-metabolic, while carbogen appears to elicit a mixed effect; the CMRO 2 reduction during hypercapnia is mitigated when including hyperoxia. These findings can be important for interpreting measurements using hypercapnic or hypercapnic-hyperoxic (carbogen) stimuli

Improved detection of cerebrovascular disease processes : Introduction to the Journal of Cerebral Blood Flow and Metabolism special issue on cerebrovascular disease

Approximately 15 million individuals suffer a stroke worldwide each year, and stroke results in death or permanent disability in two-thirds of these individuals. Due to increased knowledge and management of modifiable risk factors, stroke incidence in developed countries is declining, however remains high at just under 1 million patients per year in the United States alone. Further improving management of patients with cerebrovascular disease (CVD) ultimately will require development and clinical adoption of sensitive markers of hemodynamic and metabolic failure, as well as trials that evaluate how to interpret these markers to optimize therapies. Realizing this goal and reducing the complete burden of CVD is dependent on an improved understanding of the pathophysiological processes that underlie CVD in all stages, including sub-clinical disease processes, acute stroke, and post-stroke recovery mechanisms. This document serves as an introduction to the Journal of Cerebral Blood Flow and Metabolism special issue on cerebrovascular diseases, which is comprised of contributions from experts in each of the above stages of CVD, and outlines current standards for patient management and emerging directions that have potential for improving patient care over the next decade

Improved detection of cerebrovascular disease processes : Introduction to the Journal of Cerebral Blood Flow and Metabolism special issue on cerebrovascular disease

Approximately 15 million individuals suffer a stroke worldwide each year, and stroke results in death or permanent disability in two-thirds of these individuals. Due to increased knowledge and management of modifiable risk factors, stroke incidence in developed countries is declining, however remains high at just under 1 million patients per year in the United States alone. Further improving management of patients with cerebrovascular disease (CVD) ultimately will require development and clinical adoption of sensitive markers of hemodynamic and metabolic failure, as well as trials that evaluate how to interpret these markers to optimize therapies. Realizing this goal and reducing the complete burden of CVD is dependent on an improved understanding of the pathophysiological processes that underlie CVD in all stages, including sub-clinical disease processes, acute stroke, and post-stroke recovery mechanisms. This document serves as an introduction to the Journal of Cerebral Blood Flow and Metabolism special issue on cerebrovascular diseases, which is comprised of contributions from experts in each of the above stages of CVD, and outlines current standards for patient management and emerging directions that have potential for improving patient care over the next decade

Cortical depth dependence of the BOLD initial dip and poststimulus undershoot in human visual cortex at 7 Tesla

PurposeOwing to variability in vascular dynamics across cerebral cortex, blood-oxygenation-level-dependent (BOLD) spatial and temporal characteristics should vary as a function of cortical-depth. Here, the positive response, initial dip (ID), and post-stimulus undershoot (PSU) of the BOLD response in human visual cortex are investigated as a function of cortical depth and stimulus duration at 7 Tesla (T). MethodsGradient-echo echo-planar-imaging BOLD fMRI with high spatial and temporal resolution was performed in 7 healthy volunteers and measurements of the ID, PSU, and positive BOLD response were made as a function of cortical depth and stimulus duration (0.5-8 s). Exploratory analyses were applied to understand whether functional mapping could be achieved using the ID, rather than positive, BOLD signal characteristics ResultsThe ID was largest in outer cortical layers, consistent with previously reported upstream propagation of vasodilation along the diving arterioles in animals. The positive BOLD signal and PSU showed different relationships across the cortical depth with respect to stimulus duration. ConclusionThe ID and PSU were measured in humans at 7T and exhibited similar trends to those recently reported in animals. Furthermore, while evidence is provided for the ID being a potentially useful feature for better understanding BOLD signal dynamics, such as laminar neurovascular coupling, functional mapping based on the ID is extremely difficult. Magn Reson Med 73:2283-2295, 2015. (c) 2014 Wiley Periodicals, Inc

In vivo quantification of hyperoxic arterial blood water T-1

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 (T-1a) change with hyperoxia will influence signal quantification through mechanisms relating to elevated partial pressure of plasma-dissolved O-2 (pO(2)) and increased oxygen bound to hemoglobin in arteries (Y-a) and veins (Y-v). The dependence of T-1a on Y-a and Y-v has been elegantly characterized ex vivo; however, the combined influence of pO(2), Y-a and Y-v on T(1a)in vivo under normal ventilation has not been reported. Here, T-1a is calculated during hyperoxia in vivo by a heuristic approach that evaluates T-1-dependent arterial spin labeling (ASL) signal changes to varying gas stimuli. Healthy volunteers (n=14; age, 31.5 +/- 7.2years) were scanned using pseudo-continuous ASL in combination with room air (RA; 21% O-2/79% N-2), hypercapnic normoxic (HN; 5% CO2/21% O-2/74% N-2) and hypercapnic hyperoxic (HH; 5% CO2/95% O-2) gas administration. HH T-1a 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 +/- 13.3years) with intracranial stenosis to assess whether an HH T-1a decrease prohibited ASL from being performed in subjects with known delayed blood arrival times. Arterial blood T-1a decreased from 1.65s at baseline to 1.49 +/- 0.07s 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 +/- 8.2mL/100g/min; HH CBF=45.2 +/- 13.9mL/100g/min). It can be concluded that hyperoxic (95% O-2) 3-T arterial blood T-1aHH=1.49 +/- 0.07s relative to a normoxic T-1a of 1.65s. Copyright (c) 2015 John Wiley & Sons, Ltd

In vivo quantification of hyperoxic arterial blood water T-1

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 (T-1a) change with hyperoxia will influence signal quantification through mechanisms relating to elevated partial pressure of plasma-dissolved O-2 (pO(2)) and increased oxygen bound to hemoglobin in arteries (Y-a) and veins (Y-v). The dependence of T-1a on Y-a and Y-v has been elegantly characterized ex vivo; however, the combined influence of pO(2), Y-a and Y-v on T(1a)in vivo under normal ventilation has not been reported. Here, T-1a is calculated during hyperoxia in vivo by a heuristic approach that evaluates T-1-dependent arterial spin labeling (ASL) signal changes to varying gas stimuli. Healthy volunteers (n=14; age, 31.5 +/- 7.2years) were scanned using pseudo-continuous ASL in combination with room air (RA; 21% O-2/79% N-2), hypercapnic normoxic (HN; 5% CO2/21% O-2/74% N-2) and hypercapnic hyperoxic (HH; 5% CO2/95% O-2) gas administration. HH T-1a 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 +/- 13.3years) with intracranial stenosis to assess whether an HH T-1a decrease prohibited ASL from being performed in subjects with known delayed blood arrival times. Arterial blood T-1a decreased from 1.65s at baseline to 1.49 +/- 0.07s 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 +/- 8.2mL/100g/min; HH CBF=45.2 +/- 13.9mL/100g/min). It can be concluded that hyperoxic (95% O-2) 3-T arterial blood T-1aHH=1.49 +/- 0.07s relative to a normoxic T-1a of 1.65s. Copyright (c) 2015 John Wiley & Sons, Ltd

Arterial Spin Labeling and Blood Oxygen Level-Dependent MRI Cerebrovascular Reactivity in Cerebrovascular Disease : A Systematic Review and Meta-Analysis

BACKGROUND: The cerebrovascular reactivity (CVR) results of blood oxygen level-dependent (BOLD) and arterial spin labeling (ASL) MRI studies performed in patients with cerebrovascular disease (steno-occlusive vascular disease or stroke) were systematically reviewed. SUMMARY: Thirty-one articles were included. Twenty-three (74.2%) studies used BOLD MRI to evaluate the CVR, 4 (12.9%) studies used ASL MRI and 4 (12.9%) studies used both BOLD and ASL MRI. Thirteen studies (3 significant) found a lower BOLD CVR, 2 studies found a similar CVR and 3 studies found a higher CVR in the ipsilateral compared to the contralateral hemisphere. Nine (5 significant) out of 10 studies found a lower BOLD CVR in the ipsilateral hemispheres of patients compared to controls. Six studies (2 significant) found a lower ASL CVR in the ipsilateral compared to the contralateral hemispheres. Three out of 5 studies found a significant lower ASL CVR in the ipsilateral hemispheres of patients compared to controls. KEY MESSAGES: This review brings support for a reduced BOLD and ASL CVR in the ipsilateral hemisphere of patients with cerebrovascular disease. We suggest that future studies will be performed in a uniform way so reference values can be established and could be used to guide treatment decisions in patients with cerebrovascular disease