Thomas F. Floyd

Validation of diffuse correlation spectroscopy for muscle blood flow with concurrent arterial spin labeled perfusion MRI

Calf blood flow was measured simultaneously in healthy human subjects (n = 7) during cuff inflation and deflation using near-infrared diffuse correlation spectroscopy (DCS) and arterial spin labeled perfusion MRI (ASL-MRI). The DCS and ASL-MRI data exhibited highly correlated absolute and relative dynamic flow responses in each individual (p < 0.001). Peak flow variations during hyperemia were also significantly correlated, though more for relative (p = 0.003) than absolute (p = 0.016) flow. Repeated measurement variation was less than 8% for both modalities. The results provide much needed quantitative blood flow validation of the diffuse optical correlation method in humans.

Precision of the CASL-perfusion MRI technique for the measurement of cerebral blood flow in whole brain and vascular territories

To analyze the precision of cerebral blood flow (CBF) measurements made with continuous arterial spin labeling(CASL) perfusion magnetic resonance imaging (MRI) over experimentally relevant intervals.

Stroke After Aortic Valve Surgery Results From a Prospective Cohort

Background— The incidence and impact of clinical stroke and silent radiographic cerebral infarction complicating open surgical aortic valve replacement (AVR) are poorly characterized. Methods and Results— We performed a prospective cohort study of subjects ≥65 years of age who were undergoing AVR for calcific aortic stenosis. Subjects were evaluated by neurologists preoperatively and postoperatively and underwent postoperative magnetic resonance imaging. Over a 4-year period, 196 subjects were enrolled at 2 sites (mean age, 75.8±6.2 years; 36% women; 6% nonwhite). Clinical strokes were detected in 17%, transient ischemic attack in 2%, and in-hospital mortality was 5%. The frequency of stroke in the Society for Thoracic Surgery database in this cohort was 7%. Most strokes were mild; the median National Institutes of Health Stroke Scale was 3 (interquartile range, 1–9). Clinical stroke was associated with increased length of stay (median, 12 versus 10 days; P=0.02). Moderate or severe stroke (National Institutes of Health Stroke Scale ≥10) occurred in 8 (4%) and was strongly associated with in-hospital mortality (38% versus 4%; P=0.005). Of the 109 stroke-free subjects with postoperative magnetic resonance imaging, silent infarct was identified in 59 (54%). Silent infarct was not associated with in-hospital mortality or increased length of stay. Conclusions— Clinical stroke after AVR was more common than reported previously, more than double for this same cohort in the Society for Thoracic Surgery database, and silent cerebral infarctions were detected in more than half of the patients undergoing AVR. Clinical stroke complicating AVR is associated with increased length of stay and mortality.Background— The incidence and impact of clinical stroke and silent radiographic cerebral infarction complicating open surgical aortic valve replacement (AVR) are poorly characterized. Methods and Results— We performed a prospective cohort study of subjects ≥65 years of age who were undergoing AVR for calcific aortic stenosis. Subjects were evaluated by neurologists preoperatively and postoperatively and underwent postoperative magnetic resonance imaging. Over a 4-year period, 196 subjects were enrolled at 2 sites (mean age, 75.8±6.2 years; 36% women; 6% nonwhite). Clinical strokes were detected in 17%, transient ischemic attack in 2%, and in-hospital mortality was 5%. The frequency of stroke in the Society for Thoracic Surgery database in this cohort was 7%. Most strokes were mild; the median National Institutes of Health Stroke Scale was 3 (interquartile range, 1–9). Clinical stroke was associated with increased length of stay (median, 12 versus 10 days; P =0.02). Moderate or severe stroke (National Institutes of Health Stroke Scale ≥10) occurred in 8 (4%) and was strongly associated with in-hospital mortality (38% versus 4%; P =0.005). Of the 109 stroke-free subjects with postoperative magnetic resonance imaging, silent infarct was identified in 59 (54%). Silent infarct was not associated with in-hospital mortality or increased length of stay. Conclusions— Clinical stroke after AVR was more common than reported previously, more than double for this same cohort in the Society for Thoracic Surgery database, and silent cerebral infarctions were detected in more than half of the patients undergoing AVR. Clinical stroke complicating AVR is associated with increased length of stay and mortality. # CLINICAL PERSPECTIVE {#article-title-47}

Rapid magnetic resonance measurement of global cerebral metabolic rate of oxygen consumption in humans during rest and hypercapnia

The effect of hypercapnia on cerebral metabolic rate of oxygen consumption (CMRO2) has been a subject of intensive investigation and debate. Most applications of hypercapnia are based on the assumption that a mild increase in partial pressure of carbon dioxide has negligible effect on cerebral metabolism. In this study, we sought to further investigate the vascular and metabolic effects of hypercapnia by simultaneously measuring global venous oxygen saturation (SvO2) and total cerebral blood flow (tCBF), with a temporal resolution of 30 seconds using magnetic resonance susceptometry and phase-contrast techniques in 10 healthy awake adults. While significant increases in SvO2 and tCBF were observed during hypercapnia (P < 0.005), no change in CMRO2 was noted (P > 0.05). Additionally, fractional changes in tCBF and end-tidal carbon dioxide (R2 = 0.72, P < 0.005), as well as baseline SvO2 and tCBF (R2 = 0.72, P < 0.005), were found to be correlated. The data also suggested a correlation between cerebral vascular reactivity (CVR) and baseline tCBF (R2 = 0.44, P = 0.052). A CVR value of 6.1% ± 1.6%/mm Hg was determined using a linear-fit model. Additionally, an average undershoot of 6.7% ± 4% and 17.1% ± 7% was observed in SvO2 and tCBF upon recovery from hypercapnia in six subjects.

Oxygen-sensitive 19F NMR imaging of the vascular system in vivo

The fluorine nuclear magnetic resonance spin-lattice relaxation rate (1/T1) of the perfluorochemical blood substitute perfluorotripropylamine (FTPA) is very sensitive to oxygen tension. This presents the possibility of measuring blood oxygen tension by 19F MR imaging. We obtained oxygen-sensitive 19F NMR images of the circulatory system of rats infused with emulsified FTPA. Blood oxygenation was assessed under conditions of both air- and 100% O2-breathing. T1 relaxation times were derived from MR images using a partial saturation pulse sequence. The T1 times were compared with a phantom calibration curve to calculate average blood pO2 values in the lung, liver, and spleen. The results showed marked, organ-specific increases in blood oxygen tension when the rat breathed 100% O2 instead of air.

Functional MRI and Its Applications to the Clinical Neurosciences

Functional magnetic resonance imaging (fMRI) is an emerging methodology for studying regional brain function in vivo at relatively high spatial and temporal resolution. Because MRI methods are comparatively inexpensive and entirely noninvasive, fMRI has rapidly become one of the most popular approaches for brain mapping in cognitive and systems neuroscience. There has also been great interest in using fMRI to assist in clinical diagnosis and management, with promising demonstrations of feasibility in a number of applications. Both resting and task-specific regional brain activity can be measured, primarily utilizing alterations in regional cerebral blood flow (CBF) as a surrogate marker for neural function. This article reviews the biophysical and physiological bases of fMRI and its applications to the clinical neurosciences, with particular attention to potential challenges of fMRI under pathophysiological conditions. Carefully controlled prospective evaluation of clinical fMRI in its various potential applications will be required for fMRI to be validated as a clinically useful tool. Because the technology for fMRI is widely available, its impact could be substantial.

Skeletal Muscle Microvascular Flow in Progressive Peripheral Artery Disease : Assessment With Continuous Arterial Spin-Labeling Perfusion Magnetic Resonance Imaging

OBJECTIVES We present the novel application of continuous arterial spin-labeling (CASL) magnetic resonance imaging (MRI) for the measurement of calf muscle perfusion in subjects with progressive peripheral arterial disease (PAD). BACKGROUND Peripheral arterial disease is largely considered to be a disease of conduit vessels. The impact of PAD upon microvascular flow in the end-organ, muscle, remains unknown. Continuous arterial spin-labeling is a noninvasive MRI method capable of measuring microvascular flow and might assist in our understanding of the impact of PAD upon the microvasculature. METHODS Forty subjects with varying degrees of PAD and 17 age-matched PAD-free subjects were recruited and underwent measurement of the ankle-to-brachial index (ABI) and CASL. Peak hyperemic flow (PHF) and time-to-peak (TTP) were computed and assessed as a function of ABI and calf muscle group. RESULTS An ABI dependence was found in both PHF (p = 0.04) and TTP (p < 10(-4)). Whereas TTP increased almost immediately with increasing PAD severity, PHF was, in contrast, relatively well preserved until later stages of disease. CONCLUSIONS The CASL flow measurements correlate with disease state as measured by ABI and demonstrate preserved microvascular flow reserve in the presence of early to intermediate vascular disease.

Acute Anemia Elicits Cognitive Dysfunction and Evidence of Cerebral Cellular Hypoxia in Older Rats with Systemic Hypertension

Background:Postoperative cognitive dysfunction occurs frequently after cardiac, major vascular, and major orthopedic surgery. Aging and hypertensive cerebrovascular disease are leading risk factors for this disorder. Acute anemia, common to major surgery, has been identified as a possible contributor to postoperative cognitive dysfunction. The effect of hypoxia upon cognition and the cellular and molecular processes involved in learning and memory has been well described. Cerebrovascular changes related to chronic hypertension may expose cells to increased hypoxia with anemia. Methods:Young to aged spontaneously hypertensive rats underwent testing for visuospatial memory and learning in the Morris water maze, measurement of cerebral tissue oxygenation via tissue oxygen probe, and measurement of hypoxia-sensitive genes and proteins, under conditions of sham and experimental isovolemic anemia. Results:Acute isovolemic anemia elicited evidence of aging-dependent visuospatial working memory and learning impairment. Isovolemic anemia did not result in cerebral tissue hypoxia, when measured via tissue oxygen probe. Evidence of cellular hypoxia was, however, identified in response to the anemic challenge, as hypoxia-sensitive genes and proteins were up-regulated. Importantly, cellular hypoxic gene responses were increased with anemia in an age-dependent manner in this model of aging with chronic hypertension. Conclusions:In a translational model of chronic hypertension, clinically relevant levels of acute anemia were associated with an age-dependent visuospatial working memory and learning impairment that was matched by an age-dependent cellular sensitivity to anemic hypoxia. These data offer support for a possible link between anemic hypoxia and postoperative cognitive dysfunction in humans.

Accuracy and precision of MR blood oximetry based on the long paramagnetic cylinder approximation of large vessels

An accurate noninvasive method to measure the hemoglobin oxygen saturation (%HbO2) of deep‐lying vessels without catheterization would have many clinical applications. Quantitative MRI may be the only imaging modality that can address this difficult and important problem. MR susceptometry–based oximetry for measuring blood oxygen saturation in large vessels models the vessel as a long paramagnetic cylinder immersed in an external field. The intravascular magnetic susceptibility relative to surrounding muscle tissue is a function of oxygenated hemoglobin (HbO2) and can be quantified with a field‐mapping pulse sequence. In this work, the methods accuracy and precision was investigated theoretically on the basis of an analytical expression for the arbitrarily oriented cylinder, as well as experimentally in phantoms and in vivo in the femoral artery and vein at 3T field strength. Errors resulting from vessel tilt, noncircularity of vessel cross‐section, and induced magnetic field gradients were evaluated and methods for correction were designed and implemented. Hemoglobin saturation was measured at successive vessel segments, differing in geometry, such as eccentricity and vessel tilt, but constant blood oxygen saturation levels, as a means to evaluate measurement consistency. The average standard error and coefficient of variation of measurements in phantoms were <2% with tilt correction alone, in agreement with theory, suggesting that high accuracy and reproducibility can be achieved while ignoring noncircularity for tilt angles up to about 30°. In vivo, repeated measurements of %HbO2 in the femoral vessels yielded a coefficient of variation of less than 5%. In conclusion, the data suggest that %HbO2 can be measured reproducibly in vivo in large vessels of the peripheral circulation on the basis of the paramagnetic cylinder approximation of the incremental field. Magn Reson Med, 2009.

Evaluation of Cuff-Induced Ischemia in the Lower Extremity by Magnetic Resonance Oximetry

OBJECTIVES The aim of this study was to evaluate vascular function in the lower extremities by making direct time-course measurement of oxygen saturation in the femoral/popliteal arteries and veins during cuff-induced reactive hyperemia with magnetic resonance imaging-based oximetry. BACKGROUND Magnetic resonance imaging-based oximetry is a new calibration-free technique taking advantage of the paramagnetic nature of blood that depends on the volume fraction of deoxyhemoglobin in red blood cells. METHODS We compared post-occlusive blood oxygenation time-course of femoral/popliteal vessels in: 1) young healthy subjects (YH) (n = 10; mean ankle-brachial index [ABI] 1.0 +/- 0.1, mean age 30 +/- 7 years); 2) peripheral arterial disease (PAD) patients (n = 12; mean ABI 0.6 +/- 0.1, mean age 71 +/- 9 years); and 3) age-matched healthy control subjects (AHC) (n = 8; mean ABI 1.1 +/- 0.1, mean age 68 +/- 9 years). Blood oxygenation was quantified at 3.0-T field strength with a field mapping pulse sequence yielding the magnetic susceptibility difference between blood in the vessels and surrounding muscle tissue from which the intravascular blood oxygen saturation is computed as %HbO(2). RESULTS Significantly longer washout time (42 +/- 16 s vs. 14 +/- 4 s; p < 0.0001) and lower upslope (0.60 +/- 0.20 %HbO(2)/s vs. 1.32 +/- 0.41 %HbO(2)/s; p = 0.0008) were observed for PAD patients compared with healthy subjects (YH and AHC combined). Furthermore, greater overshoot was observed in YH than in AHC (21 +/- 8 %HbO(2) vs. 10 +/- 5 %HbO(2); p = 0.0116). CONCLUSIONS Post-occlusive transient changes in venous blood oxygenation might provide a new measure of vascular competence, which was found to be reduced in subjects with abnormal ABI, manifesting in prolonged recovery during the early phase of hyperemia.