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Yufen Chen¹, ², Todd B. Parrish¹

¹Northwestern University, Chicago, Illinois, USA

Caffeine is a widely consumed methylxanthine that acts as an antagonist to adenosine and decreases cerebral blood flow through vasoconstriction. Previous work using ultrasound has shown that there are no differences in vasoreactivity in the middle cerebral arteries; however, detailed regional analysis has not been done to date. In this study, we use a combination of arterial spin labeling and BOLD to demonstrate that caffeine does not alter vascular reactivity to CO2 in motor and visual cortices.

Anne-Catherin Zappe¹, Kamil Uludag¹, Nikos K. Logothetis¹, ²

¹Max-Planck-Institute for biological Cybernetics, Tuebingen, Germany; ²University of Manchester, Manchester, UK

The BOLD signal is sensitive to cerebral blood flow (CBF), blood volume (CBV) and oxygen extraction. In the anesthetized monkey, we observe a vasodilatory ceiling effect during inhalation of 6% CO2 where CBF or CBV are not further increased by visual stimulation. In contrast, simultaneously measured local field potential responds to the stimulation as strong as during normocapnia. As a consequence, the stimulus-induced fMRI response during 6% hypercapnia has been found to be negative reflecting only the oxygen extraction from the blood. With this method, oxygen extraction can be imaged by means of fMRI without injection of an exogenous drug.

Xiang He¹, Mingming Zhu¹, Dmitriy A. Yablonskiy¹

¹Washington University in St Louis, School of Medicine, St. Louis, USA

Measurement of brain tissue oxygen extraction fraction (OEF) can provide important information on brain functioning in health and disease. The recently proposed quantitative BOLD (qBOLD) model allows for separation of contributions to the BOLD signal from OEF and deoxygenated blood volume (DBV). The objective of this study is to validate qBOLD OEF measurements in a rat model. The qBOLD OEF results averaged across entire brain were compared with the oxygenation of venous blood samples drawn directly from the superior sagittal sinus and measured with a blood gas analyzer. The results demonstrate a very good agreement between qBOLD and direct measurements.

Feng Xu¹, Hanzhang Lu¹

¹University of Texas Southwestern Medical Center, Dallas, USA

T2-Relaxation-Under-Spin-Tagging (TRUST) MRI, a recently developed technique to quantify cerebral venous oxygenation (Yv) non-invasively, is applied to measure internal jugular veins (IJV) Yv. The blood T2 values in the IJVs were 62.8±10.6ms, corresponding to a Yv of 64.3±7.2%. Compared with sagittal sinus (SS), whose T2 is 57.9±9.1ms and Yv was 62.2±6.1%, no significant difference is found by pair t-test (p=0.13, n=12). The IJV Yv is further combined with venous flux (52.7±11.1ml/100g brain/min) acquired by phase contrast (PC) scan for eight subjects, giving whole-brain cerebral metabolic rate of oxygen (CMRO2) of 1.46± 0.20 µmol/g/min.

Eric Albert Mellon¹, Reddy Shashank Beesam¹, James E. Baumgardner¹, Arijitt Borthakur¹, Walter R. Witschey¹, Ravinder Reddy¹

¹University of Pennsylvania, Philadelphia, Pennsylvania, USA

The non-radioactive, naturally-occurring, NMR active isotope 17O can be used for the non-invasive, non-toxic, and widely-employable quantification of tissue metabolism. We demonstrate measurement of CMRO2 in pigs before recirculation. A custom circuit for precise 17O2 delivery provides a step change of mouth gas concentration. A simple model of lung mixing is presented. Analysis of arterial H217O shows the time until recirculated H217O starts to be 60-80 seconds. Indirect and direct imaging is correlated to estimate CMRO2 non-invasively during that time. Only one breath of 17O2 is used, reducing cost significantly. For indirect imaging, only a clinical 1.5T scanner is required.

Joy Liau¹, Joanna Perthen¹, Thomas T. Liu¹

¹University of California at San Diego, La Jolla, California , USA

The baseline cerebral blood flow (CBF) may influence the BOLD response amplitude through: 1) changes in the maximum BOLD response and 2) changes in the functional CBF response.  In this study, we show that changes in the functional CBF response dominate BOLD variability in subject-wise measurements while changes in the maximum BOLD response dominate in voxel-wise measurements.  These results are consistent with the theory that the oxygen extraction fraction is inversely related to resting blood flow across subjects but is relatively independent of baseline blood flow across voxels.

Hanzhang Lu¹, Uma Yezhuvath¹, Kelly Lewis-Amezcua¹

¹University of Texas Southwestern Medical Center, Dallas, USA

We have previously shown that cerebral venous oxygenation can be quantified with TRUST MRI and that stimulation-evoked fMRI signal is inversely correlated with baseline oxygenation across subjects. Here we aim to test the utility of TRUST MRI in distinguishing subject groups. Checkerboards flashing at 8Hz and 4Hz were presented to two healthy control groups, respectively. Comparison between the groups with and without using TRUST MRI showed that the inter-subject variation was substantially reduced and group separation was more significant after the normalization. These results suggest that TRUST MRI may be beneficial for fMRI studies of psychiatric and neurological disorders.

Stefano Magon¹, Gianpaolo Basso², Paolo Farace¹, Giuseppe K. Ricciardi³, Andrea Sbarbati¹, Alberto Beltramello³

¹University of Verona, Verona, Italy; ²University of Trento, Mattarello, Italy; ³Borgo Trento Hospital, University of Verona, Italy

The aim of the present study was to investigate the changes and reproducibility of BOLD signal, within and across subjects, in response to different Breath Holding (BH) durations (9, 15 or 21 seconds). The parameters of the BOLD BH-induced response (Percent Signal Change, Time To Peak, Integral of Subtended Area and the number of activated voxels) were significantly different among the three BH durations. The reproducibility of the signal is directly dependent on the duration of the BH, being better for longer BH, possibly because subject’s brain vascular reactivity is pushed toward its maximum

Knut Drescher¹, Peter Jezzard², Daniel Bulte²

¹University of Cambridge, Cambridge, UK; ²University of Oxford, Oxford, UK

Three different methods of obtaining a hypercapnic state were compared for their applicability as calibration steps for functional MRI. Breathing carbon dioxide in air, carbon dioxide in oxygen and breath holding were investigated in healthy volunteer subjects to determine the effects that each technique had on physiology, flow, BOLD signal and relaxation times. Of the three methods, breathing an increased fraction of CO2 in air proved to be the preferred option, having the fewest complications which limit the effectiveness of the models in regards to changes in arterial oxygen saturation and apparent changes in metabolism.

Stefanie Winkelmann¹, Hannes Dahnke¹, Sebastian Flacke², Martin Söhle², Ingobert Wenningmann², Attila Kovacs², Frank Träber², Juergen Gieseke³, Hans Heinz Schild², Petra Mürtz²

¹Philips Research Europe, Hamburg, Germany; ²University Hospital Bonn, Bonn, Germany; ³Philips Medical Systems, Hamburg, Germany

The effect of hypercapnia (elevated level of CO2) and hyperoxia (elevated level of O2) on the MRI signal is of major diagnostic value in the field of oncology as it gives insight into a wide range of tumor parameters, e.g. the vascular growth, hemodynamic changes in the response to treatments, vasoreactivity, vascular function and vessel maturation. This work compares the MR response of R2* and the balanced SSFP signal to hyperoxia and hypercapnia in terms of time course and sensitivity, using respiratory challenges in 5 healthy volunteers during MR imaging.