Yi Zhang¹, Hye-Young Heo¹, Dong-Hoon Lee¹, Shanshan Jiang¹, Paul Bottomley¹, and Jinyuan Zhou^1,2
1Division of MR Research, Department of Radiolgoy, Johns Hopkins University, Baltimore, Maryland, United States, ²F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States

Voxel-by-voxel CEST maps provide in vivo molecular level information that can have clinical value. However, for quantitative measures, regional average CEST measurements routinely suffice for diagnosis and or assessing treatment. A recently-developed method—spectroscopy with linear algebraic modeling or SLAM—can directly provide compartmental measurements, while offering a dramatic reduction in scan times by dropping low-SNR, high k-space phase-encoding steps depending on the number of compartments. Here, SLAM is adapted to CEST acquisitions from brain tumor studies, and shown to yield quantitatively equivalent results to standard CEST, with acceleration factors of up to 45-fold.

Nicolas Geades¹, Penny Gowland¹, and Olivier Mougin^1
1Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, United Kingdom

The study presents a new method for fitting z-spectra to physically meaningful models in a reasonable computational time, by using a look up table based on Bloch Mc-Connell simulations to estimate the relative amplitudes of the different proton pools whilst correcting for the effects of inhomogeneities and other tissues properties.

Keisuke Ishimatsu¹, Shanrong Zhang¹, Koji Sagiyama¹, Osamu Togao¹, Brenda Timmons², John Minna², and Masaya Takahashi^1
1Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, United States, ²Hamon Center for Therapeutic Oncology, Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, United States

The objective of our study is to investigate whether amide proton transfer (APT) imaging can be used for monitoring treatment responses of the lung cancer in chemotherapy. We compared temporal changes of APT signal in a non-small cell lung carcinoma with and without erlotinib which is a small molecule epidermal growth factor receptor tyrosine kinase inhibitor in mice.

Xiang Xu^1,2, Craig K. Jones^1,2, Nirbhay N. Yadav^1,2, Linda Knutsson³, Jun Hua^1,2, Rita Kalyani⁴, Erica Hall⁴, John Laterra⁵, Jaishri Blakeley⁵, Roy Strowd⁵, Prakash Ambady⁵, Martin Pomper¹, Peter Barker^1,2, Guanshu Liu^1,2, Kannie W.Y. Chan^1,2, Michael T. McMahon^1,2, Robert D. Stevens^5,6, and Peter van Zijl^1,2
1Department of Radiology, Johns Hopkins University, Baltimore, MD, United States, ²F. M. Kirby Research Center, Kennedy Krieger Institute, Baltimore, MD, United States, ³Department of Medical Radiation Physics, Lund University, Lund, Sweden, ⁴Division of Endocrinology, Diabetes, & Metabolism, Johns Hopkins University, Baltimore, MD, United States, ⁵Department of Neurology, Johns Hopkins University, Baltimore, MD, United States, ⁶Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, Baltimore, MD, United States

Recent animal studies show that D-glucose is a potential biodegradable MRI contrast agent. Here, using chemical exchange saturation transfer (CEST) MRI, we show that it is possible to detect dynamic changes in the human brain at 7T during and after infusion of D-glucose. The dynamic glucose images provide information regarding blood arterial input function (AIF), tissue perfusion and glucose transport. We present data from both healthy volunteers and a brain tumor patient with anaplastic astrocytoma showing glucose enhancement in the tumor region. This method is promising for studying perfusion properties of tumors and the brain.

Tao Jin¹, Hunter Mehrens¹, and Seong-Gi Kim^1,2
1Department of Radiology, University of Pittsburgh, Pittsburgh, PA - Pennsylvania, United States, ²Center for Neuroscience Imaging Research, Institute for Basic Science, SKKU, Suwon, Korea

Recent studies showed an increase of chemical exchange-sensitive spin-lock (CESL) MRI signal during administration of 2-deoxy-glucose (2DG). Since this CESL technique lacks molecular specificity, more studies are necessary to examine whether the signal change is caused by the transport and/or the metabolism of 2DG. The results of our in vivo study show that the CESL signal induced by administration of 2DG is strongly dependent on the injecting dose, anethesia level and brain regions. It likely contains both transport and metabolisim components and can be used as biomarker for the studied of both processes.

Ke Li^1,2, Hua Li^1,3, Zhongliang Zu^1,2, Junzhong Xu^1,2, Jingping Xie^1,2, Bruce M Damon^1,2, Mark D Does^1,2, John C Gore^1,2, and Daniel F Gochberg^1,2
1Institute of Imaging Sciences, Vanderbilt University, Nashville, TN, United States, ²Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States, ³Department of Physics and Astronomy, Vanderbilt University, Nashville, TN, United States

The conventional chemical exchange saturation transfer (CEST) imaging is always confounded by the MT asymmetry of the macromolecular proton pool and nuclear overhauser enhancement. This work describes the development of a new metric, named magnetization transfer ratio with double angle and varying duty cycles (MTRdouble,vdc), based on pulsed-CEST. A π pulse train at high duty cycle (dc) (83.8% in this work) is used to maximize exchange effects; while a 2π pulse train at low dc (20.95% in this work) is used to minimize such effects. The equivalency of this approach to an ideal continuous-wave (CW) experiment is also demonstrated.

Shu Zhang¹, Zheng Liu², Robert E. Lenkinski^1,3, and Elena Vinogradov^1,3
1Radiology, UT Southwestern Medical Center, Dallas, TX, United States, ²Advanced Imaging Research Center, Oregon Health & Science University, Portland, OR, United States, ³Advanced Imaging Research Center, UT Southwestern Medical Center, Dallas, TX, United States

In this work we demonstrate that pulses of bSSFP generate an effective RF field akin to the saturation/spin-lock RF train. Thus, bSSFP and CEST/T1rho experiments are completely analogous. While in CEST the Z component of magnetization is observed, here we are focusing on the XY component. Analysis of the off-resonance frequency dependence of bSSFP profile (bSSFPX) provides information similar to CEST. We present a theoretical treatment, confirmation by simulation, and demonstrate the proof-of-principle with an image of an exchanging agent acquired using this bSSFPX approach. This method may lead to fast acquisition and quantification approaches.

Edward A Randtke¹, Kyle Jones¹, Christy Howison¹, Julio Cárdenas-Rodríguez¹, and Mark D Pagel^1
1Biological and Medical Imaging, University of Arizona, Tucson, Arizona, United States

We have incorporated the Phase-Offset MultiPlanar (POMP) Simultaneous MultiSlice (SMS) technique into CEST-FISP MRI to create multislice acidoCEST MRI protocol that can measure extracellular pH in 3D volumes of tumor and kidney tissues. Gaussian filtering was critical for improving CEST MRI for voixelwise analysis. The pHe values in tumor and kidney tissues were measured using Bloch-McConnell fitting of CEST spectra. Although voxelwise pHe measurements have some variance, pHe analyses of tissue and sub-tissue regions have excellent precision.

Ashley Pumphrey¹, Scott Thalman², Zhengshi Yang¹, Shaojing Ye¹, and Moriel Vandsburger^1,3
1Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY, United States, ²Department of Biomedical Engineering, University of Kentucky, Lexington, KY, United States, ³Department of Physiology, University of Kentucky, Lexington, KY, United States

Using a novel cardiac chemical exchange saturation transfer (CEST) method, paraCEST labeled cells following myocardial transplantation are imaged in the mouse heart for the first time. Utilizing our recently developed cardioCEST pulse sequence we demonstrate in vivo imaging of Eu-HPDO3A labeled cells in which the contrast can essentially be "turned on" at the resonant frequency of the contrast agents exchangeable proton. With the possibility of multiple CEST contrast agents being used simultaneously, cardioCEST allows for multiplex imaging of cell tracking alongside important functional parameters of cardiac function without causing disruptive signal voids.

Nikita Oskolkov^1,2, Kannie W.Y. Chan^1,2, Xiaolei Song^1,2, Tao Yu³, Peter C.M. van Zijl^1,2, Justin Hanes³, Rangaramanujam M. Kannan³, and Michael T. McMahon^1,2
1The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, Maryland, United States, ²F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States, ³Center for Nanomedicine, Johns Hopkins School of Medicine, Baltimore, Maryland, United States

The Poly(amido amine) (PAMAM) dendritics form a class of three dimensional, macromolecular hyperbranched globular polymers also known as dendrimers. Dendrimers have been shown to be an efficient drug delivery platform as a result of their physical and chemical properties. Their controlled size and the ease of conjugation with targeting ligands, drugs and imaging agents (i.e. MRI, X-ray, PET) for production of multifunctional nanoparticles allows the use of dendrimers as theranostic agents. In this study we have prepared a dendrimer particle with increased MRI visibility, distinguishing from contrast of dendrimer core3, which allows non-invasive visual guidance of drug delivery into brain tumors through covalent conjugation of a salicylic acid (SA) analogue which displays specific high-frequency-offset CEST contrast4 to a 4th generation carboxylate-terminated dendrimer (G3.5) and evaluated brain tumor uptake in vivo.