Ashley M. Stokes¹, Sudarshan Ragunathan¹, Laura Bell¹, Ekokobe Fonkem², John Karis³, and C. Chad Quarles^1
1Neuroimaging Research, Barrow Neurological Institute, Phoenix, AZ, United States, ²Neuro-Oncology, Barrow Neurological Institute, Phoenix, AZ, United States, ³Neuroradiology, Barrow Neurological Institute, Phoenix, AZ, United States

Relative cerebral blood volume (rCBV) maps are adversely impacted by contrast agent leakage effects when acquired using gadolinium-based contrast agents, and these effects can be corrected using standard leakage correction methods. In a cohort of high-grade glioma patients, we compared leakage-corrected rCBV maps acquired using gadolinium-based contrast agents to rCBV acquired using an intravascular iron-oxide-based contrast agent. The rCBV maps from both contrast agents were similar, with high voxel-wise agreement, suggesting that leakage effects are appropriately removed from rCBV maps using standard leakage correction methods.

Ashley M. Stokes¹, Taylor Olvey¹, Leland S. Hu², Leslie C. Baxter², Laura C. Bell¹, C. Chad Quarles¹, and Lea Alhilali^3
1Neuroimaging Research, Barrow Neurological Institute, Phoenix, AZ, United States, ²Mayo Clinic Arizona, Phoenix, AZ, United States, ³Neuroradiology, Barrow Neurological Institute, Phoenix, AZ, United States

Relative cerebral blood volume (rCBV) obtained from dynamic susceptibility contrast (DSC) MRI is adversely impacted by contrast agent leakage effects in enhancing brain tumors, often necessitating multiple contrast doses. The purpose of this study is to compare dual-echo rCBV maps (single-dose) with standard rCBV maps (double-dose) in patients with high-grade gliomas using commercially available software. High agreement was observed between rCBV maps with single- and double-doses, with substantial flexibility across pulse sequence parameters. This protocol could be used to lower costs and contrast dose in clinical settings, as well as eliminate variability in perfusion methods related to contrast timing schemes.

Buse Buz Yalug¹, Ayca Ersen Danyeli^2,3, Cengiz Yakicier^3,4, M. Necmettin Pamir^3,5, Koray Ozduman^3,5, Alp Dincer^3,6, and Esin Ozturk-Isik^1,3
1Institute of Biomedical Engineering, Bogazici University, Istanbul, Turkey, ²Department of Medical Pathology, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, ³Center for Neuroradiological Applications and Reseach, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, ⁴Department of Molecular Biology and Genetics, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, ⁵Department of Neurosurgery, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey, ⁶Department of Radiology, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey

The main purpose of this study was to identify isocitrate dehydrogenase (IDH) and telomerase reverse transcriptase (TERT) promoter mutations in glioma patients using classical machine learning and convolutional neural networks (CNN) on dynamic susceptibility contrast MRI (DSC-MRI). Relative cerebral blood volume (rCBV) maps of glioma patients with different genotypes including IDH-mutant, IDH-wildtype, TERT-mutant, and TERT-wildtype were compared in tumor areas. Classical machine learning classification results were over 85% for both IDH and TERT mutations. On the other hand, CNNs were able to classify IDH mutation status with 83% and TERT mutation status with 72% accuracies.

Sudarshan Ragunathan¹, Laura C Bell¹, Ashley M Stokes¹, Ekokobe Fonkem¹, John P Karis¹, and C Chad Quarles^1
1Barrow Neurological Institute, Phoenix, AZ, United States

Multi-echo acquisition strategies have the advantage of simultaneous quantification of T1/T2* values in DCR MRI, and when combined with multiband strategies, could provide comparable spatiotemporal coverage as a single shot EPI dynamic scan. While there has been some work on SMS – SAGE acquisitions, this is potentially the first work that utilizes a SENSE reconstruction framework. We demonstrated that the CNR of MBSAGE with SENSE is similar to SAGE acquisitions, and that the dynamic CNR with respect to NAWM is on the order of or slightly higher than reported by some of the SMS-SAGE implementations in literature.

Nicholas J Sisco¹, Aimee Borazanci¹, Richard Dortch¹, and Ashley M Stokes^1
1Neuroimaging Research, Barrow Neuroimaging Innovation Center, Phoenix, AZ, United States

The objective of this study is to develop magnetic resonance imaging (MRI) biomarkers that can probe complementary vascular function and myelin content. The development of biomarker assays to quantitatively probe both perfusion and myelin content is critical to assessing acute inflammatory activity and regenerative potential. We anticipate that this biomarker will give insight into the underlying pathophysiology of reversible and irreversible myelin damage.

Katharina Witzmann^1,2, Felix Raschke^1,2, Tim Wesemann³, Mechthild Krause^1,2,4,5,6, Jennifer Linn³, and Esther G.C. Troost^1,2,4,5,6
1Helmholtz-Zentrum Dresden-Rossendorf, Institute of Radiooncology – OncoRay, Dresden, Germany, ²OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany, ³Institute of Neuroradiology, University Hospital Carl Gustav Carus and Medical Faculty of Technische Universität Dresden, Dresden, Germany, ⁴Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, ⁵National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and; Helmholtz Association / Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany, ⁶German Cancer Consortium (DKTK), Partner Site Dresden, and German Cancer Research Center (DKFZ), Heidelberg, Germany

In adjuvant radio(chemo)therapy of glioma patients, irradiation of tumor-surrounding normal tissue is unavoidable, potentially leading to long-term side-effects. We analyzed radiation-induced perfusion changes measured as relative cerebral blood volume (rCBV) in supraventricular grey and white matter regions of 17 glioma patients before and 3, 6 and 9 months after radiotherapy. After treatment, perfusion remained constant in the entire regions and after dose-separation, except for a statistically significant rCBV decrease in low-dose white matter volumes 6 months after the end of radiotherapy (p=0.008) and a trend towards increasing white and grey matter perfusion in high-dose volumes at 9 months (p<0.1).

Song'an Shang¹, Weiqiang Dou², and Jingtao Wu^3
1Nanjing First Hospital, Nanjing Medical University, Nanjing, China, ²GE Healthcare, MR Research China, Beijing, China, ³Northern Jiangsu People’s Hospital, Yangzhou, China

We investigated the aberrations in regional perfusion properties among amnestic mild cognitive impairment (aMCI) patients, patients with Parkinson’s disease with MCI (PD-MCI), and healthy control (HC) by using 3D arterial spin labeling (ASL) imaging. Our results showed that normalized cerebral blood flow (CBF) as measured by 3D ASL revealed different patterns of perfusion between aMCI and PD-MCI, probably linked to distinct neural mechanisms. Therefore, this preliminary study demonstrates that normalized CBF might provide specific perfusion information for further pathological and neuropsychological studies.

Marco Muccio, MSc¹, Lillian Walton Masters¹, Giuseppina Pilloni, PhD¹, Lauren Krupp, MD¹, Abhishek Datta, PhD², Marom Bikson, PhD³, Leigh Charvet, PhD¹, and Yulin Ge, MD^1
1Department of Radiology, NYU Grossman School of Medicine, New York City, NY, United States, ²Soterix Medical Inc., New York City, NY, United States, ³Department of Biomedical Engineering, City College of New York, New York City, NY, United States

The underlying biological mechanisms of transcranial direct current stimulation (tDCS) remain relatively uncharacterized. In this report, MRI measures for cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) of healthy controls was acquired before and during tDCS to better understand real-time neuronal response. We observed a significant increase in global CBF suggesting an increase of neuronal activity during compared to before tDCS. CMRO2 showed an increase of ~7% during tDCS compared to before tDCS. We suggest that the reported cortical excitability increase may also serve as a potential biomarker for neuronal reactivity or plasticity in many neurodegenerative diseases.

Yaoming Qu¹, Qin Qin^1,2, Haitao Wen¹, Xiaochan Ou¹, Yingjie Mei³, Weibo Chen⁴, and Zhibo Wen^1
1Radiology, Zhujiang hospital of southern medical university, Guangzhou, China, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States, ³Philips Healthcare, Guangzhou, China, ⁴Philips Healthcare, Shanghai, China

Cerebral blood volume (CBV) mapping employing velocity-selective saturation pulse trains is an emerging velocity-selective arterial spin labeling (VSASL) based method for quantifying perfusion with higher SNR. Its utility was assessed for glioma patients at 3T and corelation between histopathologic vascular proliferation and perfusion MR Imaging. VSASL based CBV mapping, in good agreement with DSC-PWI and VSASL based cerebral blood flow (CBF) mapping, showed great promise for accurate quantitative assessment and preoperative grading of brain gliomas, and further potential in the IDH genotype and vascular proliferation status predicting.

Jingting Yao¹, Benjamin Risk¹, Marijn Brummer¹, Adam Daniel Singer¹, Jeanie Park¹, and David Reiter^1
1Emory University, Atlanta, GA, United States

Microcirculatory regulation in the musculoskeletal system ensures tissue oxygenation and nutrient supply that are essential for maintaining normal muscular functions. BOLD MRI-derived mapping indices M0 and T2* have previously been established as markers of blood volume and blood oxygenation in healthy subjects. This study assesses dynamic resting-state microcirculation in the calf of healthy subjects using the wavelet coherence analysis, a time-frequency approach. Quantitative wavelet-based metrics characterizing the dynamic relationship between M0 and T2* may serve as markers of blood perfusion control and useful for characterizing degraded peripheral microvascular control in diseased population.

Jaume Coll-Font^1,2,3, Or Perlman^2,3, Shi Chen¹, Robert A Eder¹, Christian T. Farrar^2,3, and Christopher T. Nguyen^1,2,3
1Cardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Charlestown, MA, United States, ²Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, United States, ³Harvard Medical School, Boston, MA, United States

In order to acquire diffusion-weighted images (DWI) of the heart, motion compensated (M2) techniques are needed. However, these reduce the sensitivity to perfusion (D*) and hence hamper the accurate estimation of IVIM parameters. Here, we evaluate the effects of M2 to the IVIM estimates in the lower leg muscle and assess feasibility of an approach to combine DWI acquired with and without M2 to fit IVIM models. Our results show that M2 underestimates D* in the IVIM model. On the other hand, the combined approach resulted in IVIM parameter estimates similar to those obtained with standard DW MR.

Jonathan Snow¹, Mehrdad Pourfathi¹, Ian Duncan¹, Harrilla Profka¹, Stephen Kadlecek¹, Yi Xin¹, Mostafa Ismail¹, Sarmad Siddiqui¹, Luis Loza¹, Tahmina Achekzai¹, Xiaoling Jin¹, Hooman Hamedani¹, Faraz Amzajerdian¹, Federico Sertic¹, Kai Ruppert¹, Ryan Baron¹, Gabriel Unger¹, Maurizio Cereda¹, Shampa Chatterjee¹, and Rahim Rizi^1
1University of Pennsylvania, Philadelphia, PA, United States

Due to a shortage of transplantable lungs, careful preservation of viable donor lungs is of paramount importance. Ex-Vivo Lung Perfusion (EVLP) and cold static storage are two clinical techniques used to preserve donor lungs prior to transplantation. In this study, magnetic resonance spectroscopy was used to compare the ability of un-ventilated normothermic EVLP vs. cold static storage to preserve rat lungs’ ATP energy status over a 5-hour ischemic period. The EVLP model was slightly better than cold static storage at sustaining the lungs’ ATP.

Xingfeng Shao¹ and Danny JJ Wang^1,2
1Laboratory of FMRI Technology (LOFT), Mark & Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States, ²Department of Neurology, University of Southern California, Los Angeles, CA, United States

A segmented 3D diffusion prepared pseudo-continuous arterial spin labeling (DP-pCASL) sequence is proposed to acquire high resolution whole brain map of water exchange rate (kw) across the blood-brain barrier. And a new acquisition protocol is proposed which acquires DP-pCASL signals at multiple long post-labeling delays (PLDs) and allows kw to be quantified with a robust regression step and without the need for signal division or additional physiological parameter as inputs.

Ulrich Lindberg¹, Signe Sloth Madsen², Karsten Skovgaard Olsen², Kirsten Møller^2,3, Mohammad Sohail Asghar², Henrik Bo Wiberg Larsson^1,3, and Mark Bitsch Vestergaard^1
1Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Copenhagen, Denmark, ²Department of Neuroanaesthesiology, Rigshospitalet, Copenhagen, Denmark, ³Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark

The aim of this study was to investigate the short-term physiological variation in global cerebral perfusion, oxygen consumption and metabolite concentration, measured by MRI. Global cerebral oxygen consumption as well as N-acetyl-aspartate concentration remain stable over a one-week period. Global cerebral perfusion and lactate concentration was correlated, though showed decreasing within-subject correlation with increasing delay between scan session during the one-week follow-up period. These results should be carefully considered when performing longitudinal studies. In conclusion MRI does provide robust reliable measurements of global cerebral metabolism.

Elies Fuster-Garcia¹, Javier Juan Albarracín², Ivar T Hovden³, Maria del Mar Ávarez-Torres², Alex Rovira⁴, Laura Oleaga⁵, Antonio J. Revert⁶, Silvano Filice⁷, Juan Miguel García-Gómez², and Kyrre Eeg Emblem^8
1Diagnostic Phyisics, Oslo University Hospital, Oslo, Norway, ²Universitat Politècnica de València, València, Spain, ³Oslo University Hospital, Olso, Norway, ⁴Hospital Universitari Vall d'Hebron, Barcelona, Spain, ⁵Hospital Clínic, Barcelona, Spain, ⁶Hospital de Manises, Manises, Spain, ⁷Azienda Ospedaliero-Universitaria di Parma, Parma, Italy, ⁸Diagnostic Physics, Oslo University Hospital, Oslo, Norway

In this work we present a method to improve the normalization of CBV maps by using a CBV atlas of the brain. This CBV atlas was generated using 134 non-linearly registered CBV maps from NCT03439332 clinical study. The proposed normalization method generates CBV values that better correlate with the patients’ OS, reaching smaller more significant p-values (p=0.034) based on Cox regression analysis, that better differentiate between high and low survivors (AUC=0.60, p=0.007) based on Kaplan Meier analysis. 

Yong Ik Jeong¹, Gregory Christoforidis¹, Niloufar Saadat¹, Steven Roth², Marek Niekrasz¹, and Timothy Carroll^1
1University of Chicago, Chicago, IL, United States, ²University of Illinois College of Medicine, Chicago, IL, United States

After the onset of an ischemic stroke, blood flow may be restored to the affected territory via pial collateral blood vessels. In this study we investigate whether delay and dispersion corrected MR DSC perfusion can accurately measure the additional blood flow to estimate pial collaterals. The percent difference between non-corrected and corrected CBF is compared against measured pial collateral scores. The percent difference in CBF is found to be predictive of pial collateral scores. With more research, corrected MR DSC CBF may be used in the clinical setting for stroke patient management.

Daniëlle van Dorth¹, Krishnapriya Venugopal², Dirk H. J. Poot², Marion Smits², Jeroen H. J. M. de Bresser³, Juan A. Hernandez-Tamames², and Matthias J. P. van Osch^1
1C. J. Gorter Center for High-Field MRI, Radiology, Leiden University Medical Center, Leiden, Netherlands, ²Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, Netherlands, ³Radiology, Leiden University Medical Center, Leiden, Netherlands

In quantitative dynamic susceptibility contrast (DSC) MRI measurement of the arterial input function (AIF) is required. Generally, a linear relation between the R₂^(*) relaxation and the arterial contrast agent concentration is assumed (or the AIF is measured outside of an artery), although this is invalid for gradient-echo. In this study an open-source simulation tool is adapted to determine how R₂^(*) depends on contrast concentration for different physiological and MR parameters and this tool is validated by previously acquired in vitro data. The results show that sequence type (gradient-echo versus spin-echo), hematocrit and field strength all affect the relation.

Rashed Sobhan¹, Donnie Cameron^1,2, and Glyn Johnson^1
1Norwich Medical School, University of East Anglia, Norwich, United Kingdom, ²C.J. Gorter Centre for High Field MRI, Department of Radiology, Leiden University Medical Centre, Leiden, Netherlands

To estimate brain perfusion from DSC-MRI, tissues’ arterial inputs are detected considering different features of the concentration time curve (CTC) collectively. No study has explored the individual AV-discriminatory power and optimal tissue-voxel-elimination thresholds for these features. Here, the area-under-the-receiver-operating-characteristic(ROC)-curves evaluated the former, while ROC cut-offs gave the latter. Three features were more effective than others: their optimal thresholds discarded tissue-voxels with high specificity and sensitivity. The knowledge of individual AV-discriminatory powers will allow Radiologists to make more informed choices while assessing the arterial candidacy of a CTC; other sites can use this threshold detection technique as a general framework. 

Elizabeth Powell¹, Ben Dickie², Yolanda Ohene², Geoff JM Parker^1,3,4, and Laura M Parkes^2
1Centre for Medical Image Computing, Department of Computer Science, University College London, London, United Kingdom, ²Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom, ³Department of Neuroinflammation, Queen Square Institute of Neurology, University College London, London, United Kingdom, ⁴Bioxydyn Limited, Manchester, United Kingdom

Contrast-enhanced ASL (CE-ASL) has been proposed as a method for measuring blood-brain barrier (BBB) water exchange. Altering the T₁ of blood using a gadolinium-based contrast agent should allow the label location to be identified as a function of post-labelling delay time; however, the shorter T₁ of blood water leads to a trade-off between contrast dose and SNR. We show using simulations that there is an optimal T₁ of blood post-contrast that balances this trade-off. Using this information we estimate the expected accuracy and precision of BBB water exchange measurements using CE-ASL. Finally, we demonstrate the method in vivo.

Elizabeth Powell¹, Marco Battiston², and Geoff JM Parker^1,3,4
1Centre for Medical Image Computing, Department of Computer Science, University College London, London, United Kingdom, ²Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, United Kingdom, ³Department of Neuroinflammation, Queen Square Institute of Neurology, University College London, London, United Kingdom, ⁴Bioxydyn Limited, London, United Kingdom

We propose a method for quantifying water exchange across the blood-brain barrier (BBB) using diffusion-filtered exchange imaging. Careful design of the diffusion filter mitigates confounding effects from in-flowing blood water spins, and use of a two-compartment model aims to avoid known biases in the apparent exchange rate approximation. Using this approach, we optimise an acquisition protocol to provide maximum sensitivity to BBB water exchange and estimate the expected accuracy and precision of the method using simulations. The technique is then validated in a human volunteer.