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Long-Delay Arterial Spin Labeling Provides More Accurate Cerebral Blood Flow Measurements in Moyamoya Patients: A Simultaneous Positron Emission Tomography/MRI Study

Audrey P. Fan, PhD; Jia Guo, PhD; Mohammad M. Khalighi, PhD; Praveen K. Gulaka, PhD; Bin Shen, PhD; Jun Hyung Park, PhD; Harsh Gandhi, MS; Dawn Holley, BS, CNMT; Omar Rutledge, MS; Prachi Singh, PhD; Tom Haywood, PhD; Gary K. Steinberg, MD, PhD; Frederick T. Chin, PhD; Greg Zaharchuk, MD, PhD

Background and Purpose: Arterial spin labeling (ASL) MRI is a promising, noninvasive technique to image cerebral blood flow (CBF) but is difficult to use in cerebrovascular patients with abnormal, long arterial transit times through collateral pathways. To be clinically adopted, ASL must first be optimized and validated against a reference standard in these challenging patient cases.


Methods: We compared standard-delay ASL (post-label delay=2.025 seconds), multidelay ASL (post-label delay=0.7–3.0 seconds), and long-label long-delay ASL acquisitions (post-label delay=4.0 seconds) against simultaneous [O-15]-positron emission tomography (PET) CBF maps in 15 Moyamoya patients on a hybrid PET/MRI scanner. Dynamic susceptibility contrast was performed in each patient to identify areas of mild, moderate, and severe time-to-maximum (Tmax) delays. Relative CBF measurements by each ASL scan in 20 cortical regions were compared with the PET reference standard, and correlations were calculated for areas with moderate and severe Tmax delays.


Results: Standard-delay ASL underestimated relative CBF by 20% in areas of severe Tmax delays, particularly in anterior and middle territories commonly affected by Moyamoya disease (P<0.001). Arterial transit times correction by multidelay acquisitions led to improved consistency with PET, but still underestimated CBF in the presence of long transit delays (P=0.02). Long-label long-delay ASL scans showed the strongest correlation relative to PET, and there was no difference in mean relative CBF between the modalities, even in areas of severe delays.


Conclusions: Post-label delay times of ≥4 seconds are needed and may be combined with multidelay strategies for robust ASL assessment of CBF in Moyamoya disease.

(Stroke. 2017; 48: 2441–2449)


Pilot study of F-18-FSPG vs F-18-FDG PET imaging for response assessment in cancer

Sonya Park, MD; Negin Hatami, MD; Omar Rutledge, MS; Norman Koglin, PhD; Billy Loo, MD, PhD; Alice Fan, MD; Erik Mittra, MD, PhD

Objectives: F-18-FDG PET/CT is widely used for therapeutic response assessment in many cancers, although the change can vary greatly depending on the type of treatment (chemotherapy vs. immunotherapy or radiotherapy). F-18-labeled FSPG, an L-glutamate derivative, has shown to be a promising radiotracer for PET imaging of the amino acid antiporter system xC- that is involved in detoxification processes and balancing oxidative stress. This prospective pilot study is the first to evaluate the utility of F-18-FSPG PET for response assessment following therapy, in comparison to F-18-FDG.


Methods: Seven patients were enrolled in this study, including three renal cell cancer (RCC) patients treated with an investigational glutaminase inhibitor and four non-small cell lung cancer (NSCLC) patients treated with external beam radiation therapy. F-18-FDG and F-18-FSPG scans were taken within 1 month of each other, once at baseline and again after treatment. Maximum standardized uptake value (SUV) and bidimensional size were measured for up to six of the hottest lesions on each scan.


Results: A variety of treatment responses were seen. Two patients with favorable response to therapy showed similar response on F-18-FDG and F-18-FSPG scans. Of two patients who had worsening disease, one showed discordant findings with decreasing F-18-FDG but increasing F-18-FSPG uptake, while the other showed progression on both F-18-FDG and F-18-FSPG, although more new lesions were identified on the latter. Another patient had stable disease, which was demonstrated as such on F-18-FDG, but had no uptake with F-18-FSPG. Two patients have not yet had their post-treatment FSPG scans. Notably, one has multiple known hepatic metastases that were not F-18-FDG-avid or F-18-FSPG-avid.


Conclusion: This pilot study shows some similarities as well as discordance in response assessment between F-18-FDG and F-18-FSPG likely relative to their alternative mechanisms of uptake. Additional studies are needed to better understand these differences and their clinical utility.

(Journal of Nuclear Medicine. 2017; 58, Supplement 1: 118)


Design and test of a double-nuclear RF coil for H-1 MRI and C-13 MRSI at 7 T


Omar Rutledge, MS; Tiffany Kwak, MS; Peng Cao, PhD; Xiaoliang Zhang, PhD

Abstract: RF coil operation at the ultrahigh field of 7 T is fraught with technical challenges that limit the advancement of novel human in vivo applications at 7 T. In this work, a hybrid technique combining a microstrip transmission line and a lumped-element L-C loop coil to form a double-nuclear RF coil for proton magnetic resonance imaging and carbon magnetic resonance spectroscopy at 7 T was proposed and investigated. Network analysis revealed a high Q-factor and excellent decoupling between the coils. Proton images and localized carbon spectra were acquired with high sensitivity. The successful testing of this novel double-nuclear coil demonstrates the feasibility of this hybrid design for double-nuclear MR imaging and spectroscopy studies at the ultrahigh field of 7 T.

(Journal of Magnetic Resonance. 2016; 267: 15-21)


Characterization of Combat-Induced PTSD in OEF/OIF Veterans Using MEG-Based Imaging


Omar Rutledge, MS

Background: Post-traumatic stress disorder (PTSD) is a mental health disorder characterized by symptoms such as insomnia, irritability, issues with memory, difficulty concentrating, and poor decision-making abilities. With symptoms that closely resemble those of other anxiety disorders, it is very difficult to accurately diagnose. More research is needed to identify structural and functional imaging biomarkers to aid in diagnosis.

Methods: Ten right-handed male subjects (5 combat-exposed veterans, 5 healthy civilian controls) underwent magnetoencephalographic recording for this study. MEG data were acquired with a 275-channel whole-head CTF Omega 2000 system. Resting-state and tasked-based (Stroop Color-Naming Task) data were acquired. Voxel-based time-frequency analysis was subsequently performed using NUTMEG and SPM8.


Results: Significant differences were found between the two groups at rest (in delta, theta, gamma, and high-gamma neural oscillatory frequency bands) and during the Stroop Color-Naming task (in alpha, beta, and gamma, and high-gamma frequency bands).


Conclusions: Despite the small sample size, we were able to replicate some aspects of previous MEG research in veterans with PTSD. Not only does this result substantiate the use of MEG for population studies, but it also shows that PTSD is a mental disorder that is physical in nature and can be characterized through passively observing electromagnetic neuronal activity.

(Masters Thesis (2015) - University of California, San Francisco)


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