Saskia Bollmann^1,2, Michael I. Bernier^1,2, Simon Daniel Robinson^3,4,5, and Jonathan R. Polimeni^1,2,6
1Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ²Department of Radiology, Harvard Medical School, Charlestown, MA, United States, ³Centre for Advanced Imaging, The University of Queensland, Brisbane, Australia, ⁴High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ⁵Department of Neurology, Medical University of Graz, Graz, Austria, ⁶Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States

Non-invasive imaging of the pial arterial vasculature using the inflow-based contrast provided by moving blood water spins requires sufficiently small voxel sizes (160 μm) to maintain high contrast in small pial arteries (200 μm diameter). Additional acquisition of quantitative susceptibility values allows the differentiation of veins and arteries, turning magnetic resonance angiography into true arteriography. Importantly, flow compensation in all phase encoding directions is necessary to assure geometric accuracy, even for small vessels.

Weiting Zhang^1,2,3, Tzu-Hao Chao^1,2,3, Yue Yang^1,4, Tzu-Wen Wang^1,2,3, Esteban Oyarzabal^1,2,3, SungHo Lee^1,2,3, Brittany Katz^1,2,3, Guohong Cui⁵, and Yan-Yu Ian Shih^1,2,3
1Center for Animal MRI, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, ²Biomedical Research Imaging Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, ³Department of Neurology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, ⁴Department of Statistics, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States, ⁵Neurobiology Branch, NIEHS/NIH, RTP, NC, United States

The number of fiber-photometry studies incorporating fMRI are rapidly increasing, as these compatible modalities have the ability to reveal neuronal ground-truths. We recently noticed that photometry recording suffers from hemodynamic contamination, leading to false negative results. In this study, we 1) demonstrate how changes in cerebrohemodynamics can yield false negative GCaMP data, 2) propose a method to derive HbO and HbR from spectrally resolved fiber-photometry, 3) validate the derive hemodynamic parameters against concurrently measured CBV and BOLD using photometry and fMRI, 4) implement the proposed correction in vivo, and 5) apply corrected photometric results to rapidly derive hemodynamic response functions.

Jingyuan E Chen^1,2, Nina E Fultz¹, Gary Glover³, Bruce R Rosen^1,2, Jonathan R Polimeni^1,2, and Laura D Lewis^4
1Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, United States, ²Radiology, Harvard Medical School, Boston, MA, United States, ³Radiology, Stanford University, Stanford, CA, United States, ⁴Biomedical Engineering, Boston University, Boston, MA, United States

In this study, we employed concurrent EEG/fMRI to investigate the neuronal and vascular mechanisms driving task-contrast modulation of HRF shapes. Our results demonstrated that HRFs vary as a function of task contrast levels. Briefly, HRFs elicited by high-contrast stimuli exhibited delayed time-to-peaks and stronger post-stimulus undershoots that likely arose from neuronal origins, and wider full-width-at-half-maximums that were possibly driven by vascular changes. 

Jan Kufer¹, Jens Goettler^1,2,3, Samira Epp¹, Mikkel Bo Hansen⁴, Claus Zimmer¹, Kim Mouridsen⁴, Fahmeed Hyder², Christine Preibisch^1,5, and Stephan Kaczmarz^1,2
1School of Medicine, Department of Neuroradiology, Technical University of Munich, Munich, Germany, ²MRRC, Yale University, New Haven, CT, United States, ³School of Medicine, Department of Radiology, Technical University of Munich, Munich, Germany, ⁴Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark, ⁵School of Medicine, Clinic of Neurology, Technical University of Munich, Munich, Germany

The effective oxygen diffusivity (EOD) of the capillary bed has gained increasing interest as a promising biomarker providing additional information on microvascular integrity. To overcome limitations in the applicability of existing and relatively complex EOD mapping techniques, we proposed a novel more easily applicable MR-based approach. We measured EOD in 16 young and 30 elderly healthy subjects. Our measurements of EOD by MRI in young subjects yielded comparably good results in comparison with PET-data as a reference. Furthermore, we found EOD reductions in elderly healthy subjects with concomitant capillary transit-time heterogeneity (CTH) increases, indicating disturbed capillary oxygen extraction ability.

Eleonora Patitucci¹, Rachael C Stickland ², Hannah L Chandler¹, Michael Germuska¹, Catherine Foster¹, Sharmila Khot¹, Neeraj Saxena¹, Valentina Tomassini^1,3, and Richard G Wise^1,3
1CUBRIC - Cardiff University Brain Research Imaging Centre -Psychology, Cardiff University, Cardiff, United Kingdom, ²Department of Physical Therapy and Human Movement Sciences, Northwestern University, Chicago, IL, United States, ³Institute for Advanced Biomedical Technologies (ITAB), Department of Neurosciences, Imaging and Clinical Sciences, University of Chieti-Pescara “G. d’Annunzio”, Chieti, Italy

Calibrated fMRI can map the rate of cerebral oxygen consumption of the human brain, offering an important indicator of energy dysfunction in neurodegenerative and neuroinflammatory diseases. Previous studies investigated oxygen metabolism at rest or in response to tasks within BOLD signal defined region of interests (ROIs). Here, we investigate on a voxel-by-voxel basis the oxygen metabolic activity in patients with multiple sclerosis during the execution of a task. We show the feasibility of mapping task-induced CMRO₂ changes, demonstrating reduced oxygen consumption in the basal ganglia in MS patients that was not otherwise evident from BOLD or CBF signals.

Wenbo Li^1,2, Peter van Zijl^1,2, and Qin Qin^1,2
1Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

A new method is proposed to quantify the venular cerebral blood volume (vCBV) by using Fourier-transform based velocity-selective inversion (FT-VSI) to null the arterial blood signal while using Fourier-transform based velocity-selective saturation (FT-VSS) to suppress the tissue signal. Compared to previous schemes, the proposed method potentially has higher SNR and is more robust to tissue signal fluctuations attributed to system instabilities and physiological motion. The contamination of cerebrospinal fluid (CSF) signal is also corrected for by taking an extra image at a second echo with long TE. Using this method, vCBV of five volunteers were measured at 3T.

Rita Gil¹, Francisca F. Fernandes¹, and Noam Shemesh^1
1Champalimaud Neuroscience Programme, Champalimaud Centre for the Unknown, Lisbon, Portugal

We investigated BOLD responses along the rat visual pathway via inter-stimulus-intervals (ISI) and stimulus pulse width (PW) modulation. PWs did not impact negative BOLD responses (NBRs) while shortening ISI resulted in very large increases in NBRs. Visual cortex (VC) NBRs at short ISIs were accompanied by decreased positive BOLD responses (PBRs) in lateral geniculate nucleus of the thalamus (LGN) and superior colliculus (SC). At the shortest ISI (30ms) NBRs were observed in SC. Along with reported reduced visual evoked potentials amplitude at short ISIs, our findings suggest decreased net excitability as a source for negative BOLD responses in this scenario.

Rachael Stickland¹, Apoorva Ayyagari¹, Kristina Zvolanek¹, and Molly Bright^1
1Northwestern University, Chicago, IL, United States

Cerebrovascular reactivity (CVR), the blood flow response to a vasodilatory stimulus, is changed in many pathologies. CVR can be estimated without gas challenges by performing breathing tasks or by analyzing natural CO2 fluctuations at rest. We added two short breathing tasks (hypercapnic: breath hold, hypocapnia: cued deep breathing) to the start of two resting state fMRI scans. When using all the data, or just the breathing segments, adequate CVR maps could be estimated; this was not the case when just using the resting portions. This paradigm can provide an estimate of CVR, and help improve analysis of resting state data.

Stephan Kaczmarz^1,2, Jan Kufer¹, Lena Schmitzer¹, Jens Göttler^1,2,3, Mario Eduardo Archila Melendez¹, Andreas Hock⁴, Christian Sorg¹, Claus Zimmer¹, Fahmeed Hyder², and Christine Preibisch^1,5
1School of Medicine, Department of Neuroradiology, Technical University of Munich, Munich, Germany, ²MRRC, Yale University, New Haven, CT, United States, ³School of Medicine, Department of Radiology, Technical University of Munich, Munich, Germany, ⁴Philips Healthcare, Hamburg, Germany, ⁵School of Medicine, Clinic of Neurology, Technical University of Munich, Munich, Germany

Calibrated-fMRI is highly promising to quantify human brain function via mapping changes of cerebral metabolic rate of oxygen. While the R₂’-based approach is easily applicable, systematic differences to the well-established hypercapnia-calibration have been reported. We present data from an ongoing study in seven healthy young subjects correlating calibration factors M from R₂' vs. hypercapnia. We hypothesized better correlation after methodological improvements in R₂'-mapping and pseudo-continuous arterial spin labeling (pCASL). Our results confirmed this hypothesis, with good correlations between both fMRI-calibrations. However, we found potentially confounding hypercapnia effects on pCASL. Thus, our results suggest benefits of gas-free R₂’-calibration for future applications.

Joseph R Whittaker¹, Jessica Steventon¹, Marcello Venzi¹, and Kevin Murphy^1
1CUBRIC, School of Physics and Astronomy, Cardiff University, Cardiff, United Kingdom

The Thigh Cuff Challenge (TCC) technique is a promising method for assessing dynamic cerebral autoregulation with fMRI. A TCC fMRI experiment was performed in order to better understand the BOLD fMRI signal changes associated with autoregulation. We demonstrate that TCC event-locked cortical fMRI signal changes are widespread across cortical grey matter, with varying response shape both within and between subjects. The TCC BOLD response is on average ~0.3%, which we estimate on a voxel-wise basis using a novel informed basis set, which provides a proof-of-concept demonstrating the potential of TCC and fMRI to probe cerebrovascular function.

Hyun Seok Moon^1,2, Haiyan Jiang¹, Won Beom Jung^1,2, JungMi Lee¹, Gunsoo Kim¹, and Seong-Gi Kim^1,2
1Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon, Korea, Republic of, ²Department of Biomedical Engineering, Sungkyunkwan University, Suwon, Korea, Republic of

BOLD fMRI combined with optogenetics allows for brain-wide neural network studies. Most studies have focused on activity of excitatory neurons, which is presumably to contribute BOLD fMRI dominantly. However, fMRI response evoked by inhibitory neural activities is unknown. Here, we investigated 15.2T BOLD response of optogenetically stimulated GABAergic neural activation, and verified the results with electrophysiology.

Carola Canella^1,2, Federico Rocchi^1,2, Shahryar Noei³, Daniel Gutierrez-Barragan¹, Ludovico Coletta¹, Elizabeth de Guzman¹, Alberto Galbusera¹, Massimo Pasqualetti⁴, Giuliano Iurilli⁵, Stefano Panzeri³, and Alessandro Gozzi^1
1Functional Neuroimaging Laboratory, Istituto Italiano di Tecnologia, Rovereto, Italy, ²Center for Mind and Brain Sciences, University of Trento, Rovereto, Italy, ³Neuronal Computational Laboratory, Istituto Italiano di Tecnologia, Rovereto, Italy, ⁴Biology Department, University of Pisa, Pisa, Italy, ⁵Systems Neurobiology Laboratory, Istituto Italiano di Tecnologia, Rovereto, Italy

Neuroimaging measurements of functional connectivity are commonly interpreted as an index of reciprocal interareal communication. However, direct testing of this hypothesis has been lacking. Using chemogenetics, electrophysiology and resting-state fMRI in the mouse, we show that acute and chronic silencing of the prefrontal cortex result in paradoxical rsfMRI overconnectivity of the mouse default mode network (DMN) and increased delta activity, an effect relayed to wider cortical territories by polymodal thalamic areas. Our results challenge prevailing interpretations of functional connectivity and implicate a critical contribution of sub-cortical rhythm generators to the establishment of large-scale functional coupling.

Marlon Pérez-Rodas^1,2, Hildegard Schulz¹, Rolf Pohmann¹, Klaus Scheffler^1,3, and Rahel Heule^1
1High-Field MR Center, Max Planck Institute for Biological Cybernetics, Tübingen, Germany, ²Graduate Training Centre of Neuroscience, IMPRS for Cognitive and Systems Neuroscience, University of Tübingen, Tübingen, Germany, ³Department of Biomedical Magnetic Resonance, University of Tübingen, Tübingen, Germany

To fully understand the neurovascular fingerprint observed in BOLD experiments, extravascular and intravascular contributions have to be identified separately. Balanced steady-state free precession (bSSFP) imaging has demonstrated the ability for distortion-free fMRI with high microvascular sensitivity. However, the underlying intravascular contribution to BOLD bSSFP is not yet entirely known as literature R₂ relaxation rates do not reflect the apparent diffusion-related R₂ decrease in blood with shorter bSSFP refocusing intervals (TRs). This work thus focuses on characterizing the oxygen sensitivity of bSSFP in blood samples at high to ultra-high fields by means of passband signal differences and intrinsic R₂ estimation.

Yury Koush¹, Robin A. de Graaf¹, Peter Herman¹, Douglas L. Rothman¹, and Fahmeed Hyder^1
1Yale University, New Haven, CT, United States

Resting-state fMRI studies are conducted with eyes-closed (EC) or eyes-open (EO) conditions. Given differences in spontaneous activity between EO and EC conditions, metabolic foundations of fMRI-derived networks, specifically activated (e.g., sensory network) and deactivated (e.g., default mode network, DMN) nodes, are poorly understood. We assessed aerobic glycolysis and excitatory-inhibitory balance in healthy volunteers’ visual cortex (VC, a non-DMN node) and posterior cingulate cortex (PCC, a DMN node) using J-edited fMRS and calibrated fMRI. Functional changes between EO and EC conditions are regionally non-specific to aerobic glycolysis and flow-metabolism coupling, but neurovascular coupling in VC depends on EO and EC conditions.