3D Real-Time Magnetic Particle Imaging of Cerebral Blood Flow in Living Mice
Jürgen Rahmer¹, Bernhard Gleich¹, Jürgen Weizenecker², Jörn Borgert^1
1Philips Technologie GmbH, Forschungslaboratorien, Hamburg, Germany; ²University of Applied Sciences, Karlsruhe, Germany

The cerebral blood flow of living mice is imaged in real-time using magnetic particle imaging (MPI). This new medical imaging modality allows rapid imaging of 3D iron oxide nanoparticle distributions without anatomical background signal. For the experiments, an iron-oxide agent was bolus injected into the tail vein at clinically approved dosages.

Simultaneous Assessment of Perfusion with [¹⁵O]water PET and Arterial Spin Labeling MR Using a Hybrid PET/MR Device
Hans F. Wehrl¹, Martin S. Judenhofer¹, Florian C. Maier¹, Petros Martirosian², Gerald Reischl³, Fritz Schick², Bernd J. Pichler^1
1Laboratory for Preclinical Imaging of the Werner Siemens-Foundation, University of Tuebingen, Tuebingen, BW, Germany; ²Section on Experimental Radiology, University of Tuebingen, Tuebingen, BW, Germany; ³Radiopharmacy and PET-Center, University of Tuebingen, Tuebingen, BW, Germany

PET/MR imaging is an emerging technology. In this study, for the first time, PET as well as MR-ASL perfusion data were acquired simultaneously with a small animal PET/MR device, therefore minimizing confounding parameters such as physiological variations between the scans. Absolute [¹⁵O]water PET and MR perfusion data were compared, and discussed in respect to blood-brain-barrier permeability issues. Permeability surface (PS) product values for different brain areas were determined. These experiment show an excellent application of PET/MR for cross-validation studies and pave the way for a wider range of multifunctional-imaging studies.

Estimation of CBF Based on the Metabolic H₂¹⁷O Decay Rate in CMRO₂ Measurement Using In Vivo ¹⁷O MR Approach - not available
Xiao-Hong Zhu¹, Yi Zhang¹, Hannes Wiesner², Kamil Ugurbil¹, Wei Chen^1
1Center for Magnetic Resonance Research, Department of Radiology, Minneapolis, MN, United States; ²High-Field Magnetic Resonance Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany

In vivo ¹⁷O MRS imaging (MRSI) approach at high/ultrahigh field has been used to non-invasively mapping the cerebral metabolic rate of oxygen (CMRO₂) in small animals. However, imaging the cerebral blood flow (CBF) using the same ¹⁷O MR approach requires invasive procedures for introducing the NMR-visible H₂¹⁷O as exogenous tracer. In the present study, we demonstrate that the decay rate of the metabolic H₂¹⁷O water following a brief ¹⁷O₂ gas inhalation in the CMRO₂ measurement, although does not directly reflect the CBF value, is closely related to brain perfusion. A linear relationship between CBF and corresponding metabolic H₂¹⁷O decay rate has been determined experimentally from combined CBF and CMRO₂ measurements in rat brains under varied physiological conditions. The outcomes of the study indicate that in vivo ¹⁷O MRS/MRSI approach is a useful tool for noninvasively assessing not only CMRO₂ but also CBF simultaneously in the rat brain; and it provides new utilities for studying the cerebral oxygen metabolism and tissue perfusion associated with brain function and dysfunction.

Hippocampal Blood Flow and Vascular Reactivity in Normal Aging
Henry Rusinek¹, Lidia Glodzik², Miroslaw Brys³, Francois Haas⁴, Kellyanne Mcgorty¹, Qun Chen¹, Mony J. de Leon^2
1Radiology, New York University School of Medicine, New York, NY, United States; ²Psychiatry, New York University School of Medicine, New York, NY, United States; ³Neurology, New York University School of Medicine, New York, NY, United States; ⁴Medicine, New York University School of Medicine, New York, NY, United States

Hippocampal blood flow and vascular reactivity were measured in 34 normal subjects aged 26-92 years using pulsed ASL with segmented TrueTFISP readout. Test-retest studies indicate reproducibility averaging 3.6 ml/100g/min (5.4%). Hippocampal flow averaged 61.2±9.0 ml/100g min, with no age effect. The cortical flow averaged 57.2±10.4 ml/100g min and there was a significant linear relationship with age. Mild hypercapnia resulted in a significant CBF increase in all brain tissue. The flow response was 18.0±12.2 in neocortex and 14.1±10.8 in the hippocampus. The cortical flow response among the women was significantly larger than in men, confirming numerous prior studies.

Sensitivity of CASL MRI to Quantitative Regional and Global Changes Associated with Pain
Michael Froelich¹, Hrishikesh Deshpande², Tim J. Ness¹, Beverly Corbitt², Rajiv Menon³, Jan den Hollander⁴, Georg Deutsch^5
1Anesthesiology, University of Alabama at Birmingham, Birmingham, AL, United States; ²Radiology, University of Alabama at Birmingham, Birmingham, AL, United States; ³Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL, United States; ⁴Vascular Cardiology, University of Alabama at Birmingham, Birmingham, AL, United States; ⁵Radiology, University of Alabama at Birmingham, Birmingham, AL, United States

The imaging of cerebral activity associated with pain and painful states has important implications for the study of clinical pain syndromes, including potentially providing objective biomarkers in studies complicated by the ambiguities of subjective report. We present preliminary data showing quantitative rCBF changes using CASL based rCBF in normal subjects during three pain conditions involving heat, ischemic and cold presser pain conditions.  Robust changes were recorded in thalamic and peri-rolandic as well as in mean hemispheric cortical rCBF during each condition, with the cold presser task inducing significantly greater absolute increases in thalamic and mean cortical activity.

Opioid-Induced Changes in Cerebral Blood Flow in the Human Brain During Controlled Breathing
Richard G. Wise¹, Anna Jolly², C John Evans¹, Kevin Murphy¹, Fernando Zelaya³, David Lythgoe³, Kyle Pattinson⁴, Judith E. Hall^2
1CUBRIC, School of Psychology, Cardiff University, Cardiff, United Kingdom; ²Department of Anaesthetics and Intensive Care Medicine, School of Medicine, Cardiff University, Cardiff, United Kingdom; ³Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College, London, United Kingdom; ⁴Nuffield Department of Anaesthetics, Oxford University, Oxford, United Kingdom

We show that pulsed ASL is sensitive to opioid administration in the human brain. We measured the effects of a μ-opioid (remifentanil) on regional CBF. By training volunteers to maintain their breathing, we mitigated the global CBF increases arising from increased arterial carbon dioxide levels that result from opioid-induced respiratory depression. Significant localised opioid-induced CBF increases were observed in the thalamus and brainstem, whereas, decreases were observed in the putamen: all areas rich in opioid receptors. The regionally specific nature of the opioid’s effect on CBF will be useful in interpreting opioid-related changes in task-related activity with FMRI.

ASL PhMRI After a Single Dose of Oral Citalopram
Yufen Chen¹, Hong I. Wan², John P. O'Reardon³, Marc Korczykowski¹, Ze wang¹, Jiongjiong Wang¹, John A. Detre^1
1Center of Functional Neuroimaging, University of Pennsylvania, Philadelphia, PA, United States; ²Clinical Translational Medicine, Pfizer Inc, Collegeville , PA, United States; ³Department of Psychiatry, University of Pennsylvania, Philadelphia, PA, United States

Arterial spin labeling (ASL) is a favorable alternative to blood-oxygenation-level-dependent (BOLD)–based pharmacological MRI (phMRI) as it offers an easily interpreted, quantitative measurement of cerebral blood flow (CBF). We investigate the feasibility of ASL phMRI to detect the effects of a single orally administered dose of citalopram—a commonly used antidepressant—in healthy subjects. Our results reveal a significant drug-induced reduction in CBF within the amygdala. This result is in agreement with prior studies that show a correlation between amygdala function and depression, and indicates that ASL phMRI is a valuable tool for clinical trials.

Sustained Cerebral Hypoxia Increases Cerebral O2 Metabolism
Erin Krizay¹, John S. Hunt Jr. ¹, Ethan Li¹, Billy C. Hsu¹, David D. Shin¹, Zachary Smith¹, Richard B. Buxton¹, Miriam Scadeng¹, David J. Dubowitz^1
1Radiology, University of California San Diego, La Jolla, CA, United States

Hypoxia results in decreased arterial oxygenation to the brain and increased cerebral blood flow. Previous studies suggest moderate global hypoxia does not influence resting cerebral oxygen metabolism (CMRO2), yet basal metabolic rate increases with sustained hypoxia. We examined the effects of 2 and 7 days of sustained global hypoxia on CMRO2 from measurements of venous T2 (using TRUST MRI), resting CBF (using ASL MRI), and SaO2 and Hb. Following 2 days hypoxia, CMRO2 increased by 59% to 2.5 mmol/g/min (+/- 0.9, p<0.01). Following 7 days hypoxia, CMRO2 increased 36% relative to normoxia, to 2.2 mmol/g/min (+/- 0.8, p<0.05).

Layer-Specific Blood-Flow and BOLD FMRI of the Mouse Retina Associated with Hypoxic Challenge
Eric Raymond Muir^1,2, Qiang Shen², Timothy Q. Duong^2
1Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA, United States; ²Research Imaging Institute, Ophthalmology/Radiology, UT Health Science Center San Antonio, San Antonio, TX, United States

The retina has two separate blood supplies, the retinal and choroidal vessels, located on either side of the retina. We recently showed that MRI at 42x42 µm can resolve layer-specific blood flow (BF) in both vascular layers, and the avascular layer in between in mice. In this study, we further developed this BF MRI technique to include inversion-recovery suppression of the vitreous and applied it to image layer-specific BF and BOLD changes during hypoxic challenge in mouse retinas. Basal BF and BF and BOLD responses to mild hypoxic challenge were markedly different between the retinal and choroidal vasculatures.

Effect of Hematocrit on MR Estimates of BVf, VSI and Local Blood Oxygen Saturation. an in Vivo Study
Thomas Christen¹, Benjamin Lemasson¹, Nicolas Pannetier¹, Regine Farion¹, Christoph Segebarth¹, Chantal Remy¹, Emmanuel Louis Barbier^1
1INSERM U836, Grenoble, France

We have investigated the influence of the hematocrit on the MR estimates of Blood Volume fraction (BVf), Vessel Size Index (VSI) and local SO2 (lSO2). In healthy rats, the hematocrit was either decreased using isovolumic hemodilution or increased using an intermittent hypoxia preconditionning. Measurements obtained with MR were compared to quantitative histology and blood gas analysis. Our results showed variations of lSO2 (consistent with a stable tissue oxygenation level), variations of BVf and no changes in VSI between groups of animals. In all cases MRI and biology remains correlated suggesting a linear effect of hematocrit on the MR estimates.