REGIS OTAVIANO FRANCA BEZERRA¹, Hae Won Lee², Gustavo Kaneblai³, Eduardo Figueiredo³, Mitsuharu Miyoshi⁴, Thomas Doring³, Claudia da Costa Leite⁵, Giovanni Guido Cerri², and Frederico Perego Costa^6
1RADIOLOGY, HOSPITAL SÍRIO-LIBANÊS, SAO PAULO, Brazil, ²Radiology, Hospital Sírio-Libanês, Sao Paulo, Brazil, ³General Eletric, Sao Paulo, Brazil, ⁴General Eletric, Tokyo, Japan, ⁵RADIOLOGIA, HOSPITAL SÍRIO-LIBANÊS, SAO PAULO, Brazil, ⁶Oncology, Hospital Sírio-Libanês, Sao Paulo, Brazil

This study shows the glucoCEST effect in 15 patients with primary malignant brain tumors compared with normal white matter(NWM) at 3-Tesla-MRI. The procedure included a full Z-spectra CEST and a dynamic glucoCEST. The signal % at 2 ppm calculated using mean asymmetric magnetization transfer ratio values were significantly higher in the whole cancer compared to NWM. Similarly, the dynamic glucoCEST presented as mean area-under-the-curve values were significantly different in whole cancer in comparison to normal tissue. This method, using clinical field strength of 3Tesla, was capable of identifying distinct patterns of glucose metabolismand also heterogeneity in the cancer metabolism

Alexey Samsonov¹ and Aaron S. Field^1
1Radiology, University of Wisconsin-Madison, Madison, WI, United States

We study the effect of macromolecular proton fraction (MPF) and R1 interdependency in quantitative MT experiments. We hypothesize that the two-pool model with properly calibrated relaxation constraints on the bound proton pool can separate interdependency of both metrics, potentially improving the specificity of both, specifically, MPF to macromolecular content and R1 to paramagnetic ions. The simulation and in vivo results support feasibility of such refinement.

Manuel Taso¹, Fanny Munsch¹, Olivier M Girard², Guillaume Duhamel², David C Alsop¹, and Gopal Varma^1
1Division of MRI research, Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States, ²CRMBM, Aix-Marseille Univ, CNRS, Marseille, France

3D myelin imaging using inhomogeneous magnetization transfer (ihMT) has seen increased interest as sequence implementations evolve. This has mostly been based on prepared or pseudo-steady-state gradient echo sequences. However, Fast-Spin-Echo (FSE) sequences should have a theoretical SNR advantage over GRE. Here we report implementation of  a CSF-suppressed FSE sequence for ihMT imaging (FLAIR-ihMT), exploring through simulations the effect of CSF suppression and providing first imaging results, highlighting the benefits of CSF suppression, potential for whole brain high-resolution imaging and translation down to the spinal cord.  

Sarah Rosemary Morris^1,2,3, Irene M. Vavasour^1,4, Anastasia Smolina^5,6, Erin MacMillan^4,7, Guillaume Gilbert⁷, Michelle Lam^2,4, Piotr Kozlowski^1,2,4,8, Carl Michal², Alan Manning², Alex L. MacKay^1,2,4, and Cornelia Laule^1,2,4,8,9
1Radiology, University of British Columbia, Vancouver, BC, Canada, ²Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada, ³International Collaboration on Repair Discoveries, Vancouver, BC, Canada, ⁴UBC MRI Research Centre, Vancouver, BC, Canada, ⁵Physics & Astronomy, McMaster University, Hamilton, ON, Canada, ⁶Hospital for Sick Children, Toronto, ON, Canada, ⁷MR Clinical Science, Philips Healthcare Canada, Markham, ON, Canada, ⁸International Collaboration on Repair Discoveries (ICORD), Vancouver, BC, Canada, ⁹Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

We compared three myelin-sensitive MRI metrics (inhomogeneous magnetization transfer ratio (ihMTR), magnetization transfer ratio (MTR) and gradient and spin echo-derived myelin water fraction (MWF)) in 15 white matter regions of interest from 14 healthy adults at 3T. Reproducibility of ihMTR was also investigated. We found a moderately strong correlation between MWF and ihMTR but only a very weak correlation between MWF and MTR. Myelination rankings were similar for ihMTR and MWF but had no relation to MTR. Finally, we established an average ihMTR scan-rescan variability of 8.2% of the mean in each ROI.

Ravi Prakash Reddy Nanga¹, Elizabeth A Rosenfeld², Deepa Thakuri¹, Mark Elliott¹, Ravinder Reddy¹, and Diva D De Leon^2
1Radiology, University of Pennsylvania, Philadelphia, PA, United States, ²Endocrinology and Diabetes, Children’s Hospital of Philadelphia, Philadelphia, PA, United States

Hyperinsulinism/Hyperammonemia (HI/HA) syndrome is an orphan disease characterized by fasting and protein-induced hypoglycemia, hyperammonemia, and has high prevalence of epilepsy, developmental delays, and learning disabilities. Understanding the mechanism involved in brain phenotype remains limited. We have previously shown the application of glutamate weighted chemical exchange saturation transfer (GluCEST) imaging in small set of subjects to spatially map the glutamate levels of hippocampus. In this study we have expanded the human subject pool for studying the abnormal function of glutamate dehydrogenase (GDH) enzyme activity with HI/HA syndrome.

Lok Hin LAW¹, Peng XIAO¹, Jianpan Huang¹, Xiongqi HAN¹, and Kannie WY CHAN^1,2,3
1Department of Biomedical Engineering, City University of Hong Kong, Hong Kong, Hong Kong, ²Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ³City University of Hong Kong Shenzhen Research Institute, Shenzhen, China

Imaging-guided nose-to-brain drug delivery provide a non-invasive monitoring of drug delivery to brain, which increases effective dose via bypassing Blood-Brain-Barrier(BBB). Here, we investigated imaging of nanomedicine delivery via intranasal-administration using CEST-detectable mucus-penetrating-liposome(with 10%PEG). Liposomes were loaded with Iohexol(Ioh-Lipo) and CEST properties were examined both in-vitro and in-vivo by injecting into mouse nostril. Ioh-Lipo generated CEST contrast of 33.4% at 4.3 ppm in-vitro. which was also observed in nostril, olfactory-bulb and frontal-lobe after intranasal-administration at 3T. We demonstrated the liposomes detectability both in nostril and olfactory-bulb by CEST. The result demonstrates an approach for imaging-guided Nose-to-Brain Intranasal Liposomal Drug Delivery.

Shanshan Jiang¹, Pengfei Guo², Hye Young Heo¹, Peter van Zijl^1,3, and Jinyuan Zhou^1
1Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, ²Whiting School of Engineering, Johns Hopkins University, Baltimore, MD, United States, ³F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, United States

Assessing post-treatment malignant gliomas early has remained one of the most critical dilemmas in neuro-oncology for three decades. Amide protein transfer weighted (APTw) MRI has been validated to accurately detect recurrent malignant gliomas in more and more studies. The peritumoral area, as the one of the most aggressive regions, has been seldom studied. Here, we explore radiomics features extracted from peritumoral areas on APTw images to unveil the progressive pattern in early recurrent malignant gliomas. Our results suggest that the use of APTw radiomic features can add important value to structural MRI to assess the treatment response.

Celine Taglang¹, Georgios Batsios¹, Mers Tran¹, Anne Marie Gillespie¹, Hema Artee Luchman², Russell O Pieper³, Sabrina M Ronen¹, and Pavithra Viswanath^1
1Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, United States, ²Cell Biology and Anatomy, University of Calgary and Hotchkiss Brain Institute, Calgary, AB, Canada, ³Neurological Surgery, University of California San Francisco, San Francisco, CA, United States

²H-magnetic resonance spectroscopy (MRS) recently emerged as a novel, non-invasive method of monitoring metabolic fluxes in high-grade glioblastomas in vivo. However, its utility for imaging low-grade gliomas and for assessing treatment response has not been examined. Here, we show that [6,6’-²H]-glucose metabolism to lactate serves to delineate tumor from contralateral normal brain in mice bearing orthotopic patient-derived low-grade glioma xenografts. Importantly, reduced lactate production from [6,6’-²H]-glucose informs on early response to therapy, at timepoints when volumetric alterations cannot be detected by anatomical imaging, pointing to the ability of [6,6’-²H]-glucose to assess pseudoprogression, which is a major challenge in glioma imaging.

Gilbert Hangel¹, Philipp Lazen², Matthias Tomschik¹, Jonathan Wais¹, Eva Hečková², Lukas Hingerl², Stephan Gruber², Bernhard Strasser², Gregor Kasprian³, Daniela Prayer³, Julia Furtner³, Christoph Baumgartner⁴, Johannes Koren⁴, Robert Diehm⁵, Martha Feucht⁵, Christian Dorfer¹, Ekaterina Pataraia⁶, Wolfgang Bogner², Siegfried Trattnig^2,7, and Karl Rössler^1
1Department of Neurosurgery, Medical University of Vienna, Vienna, Austria, ²High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ³Division of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, ⁴Department of Neurology, Clinic Hietzing, Vienna, Austria, ⁵Department of Paediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria, ⁶Department of Neurology, Medical University of Vienna, Vienna, Austria, ⁷Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria

We successfully implemented a fast high-resolution 3D-MRSI protocol covering the whole brain at 7T in a preliminary study of 14 patients with pharmacoresistant epilepsy. With an isotropic resolution of 3.4 mm acquired in 15:30 min, we detected focal metabolic alterations in thirteen patients. From all metabolites, tCr, Glu, mIns and NAA and especially tCho appear as the most relevant markers for detection of focal metabolic alterations in epilepsy. Especially concerning cortical developmental alterations as a cause of epilepsy, our findings may have the potential to differentiate metabolic fingerprints for FCD subclasses.

Florence Fauvelle^1,2, Vasile Stupar^1,2, Jia Guo³, Wafae Labriji¹, Chen Liu³, Alicia Plaindoux¹, Emmanuel Luc Barbier^1,2, Sophie Hamelin¹, and Antoine Depaulis^1
1Grenoble Institut Neurosciences, University Grenoble Alpes, La Tronche, France, ²IRMaGE, University Grenoble Alpes, La Tronche, France, ³Departement of Psychiatry, Columbia University, New York, NY, United States

New non invasive methods are required to better delimit the epileptogenic zone (EZ) during the pre-surgical exam of epileptic patients. By combining ex vivo NMR spectroscopy-based (MRS) untargeted metabolomics and in vivo MRS-based targeted metabolomics, we found that GABA was the most discriminant metabolite of the epileptogenic zone vs adjacent brain regions in a mouse model of mesio-temporal lobe epilepsy (MTLE). GABA appears therefore as a specific in vivo biomarker of EZ in MTLE.