Download Basic Physics and Scientific Application of CEST

ICMRI2017
March 23-25, 2017 | Grand Hilton Hotel, Seoul, Korea
Asian Forum Session 2: CEST/MT
SY21-1
Basic Physics and Scientific Application of CEST
Hiroyuki Kabasawa
MR collaboration and Development, GE Healthcare, Hino, Tokyo, Japan
Water molecule as well as other species in biological tissue is not static, but dynamically moving and chemically exchanging
each other. CEST (chemical exchange dependent saturation transfer) is a method to measure chemical exchange with NMR
technique. Chemical exchange measurement using saturation transfer has been used in NMR field long time to understand
detail molecular structure and dynamics since early days.
Basic pulse sequence design for CEST imaging is relatively simple. It includes continuous RF irradiation at certain frequency,
followed by imaging acquisition. RF irradiation should be long enough (typically seconds) to generate sufficient saturation
effect and its transfer by chemical exchange process. The continuous RF pulse saturates spins at its resonance frequency. If the
spins have any interaction with free water, spin saturation effect is transferred to free water by spin exchange and that results in
decreased water proton signal. This contrast mechanism makes us possible to perform indirect signal measurement of
unobservable molecule using conventional MRI. CEST has a large potential to provide molecular dependent contrast
mechanism, including amide proton, glucosaminoglycans, glucose and OH-containing molecules. As the Chemical exchange is
associated with pH, pH measurement using CEST has been investigated and reported.
MTR asymmetry index is frequently used to measure CEST effect. It is simple index to observe CEST effect and is easy for
interpretation. However, the MTR asymmetry is qualitative information and is contaminated with a lot of other information
other than chemical exchange. As the actual observed signal change includes not only chemical exchange, but also
magnetization transfer, and NOE effect. Z-spectrum includes such spin interaction information. More detail Z-spectrum
analysis will provide us various quantitative chemical exchange information. We have developed new CEST spectrum analysis
method called CPE-spectrum. It is robust spectrum analysis method that enable us to map out several useful information from
CEST measurement.
This presentation will cover the overview physics background of the CEST, engineering requirement for pulse sequence and
MRI system, CEST data analysis method and its application to quantitative analysis.
Keywords : CEST, Physics, Engineering
ICMRI2017
March 23-25, 2017 | Grand Hilton Hotel, Seoul, Korea
Asian Forum Session 2: CEST/MT
SY21-2
Ultrafast CEST
Jaeseok Park
Biomedical Engineering, Sungkyunkwan University, Suwon, Korea
This talk is to present ultrafast chemical exchange saturation transfer magnetic resonance imaging. We present how to design
ultrafast CEST pulse sequence to acquire full z-spectra in the whole brain, how to reconstruct the whole brain CEST images,
and how to produce corresponding asymmetric z-spectra. We expect to complete z-spectrum acquisition in clinically acceptable
imaging time and asymmetric z-spectra without conventional subtraction.
Keywords : MRI, Ultrafast, CEST
ICMRI2017
March 23-25, 2017 | Grand Hilton Hotel, Seoul, Korea
Asian Forum Session 2: CEST/MT
SY21-4
CEST Imaging of Brain Tumor
Takashi Yoshiura, Kiyohisa Kamimura, Masanori Nakajo
Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan
Chemical exchange saturation transfer (CEST) is a novel MR contrast mechanism based on the saturation transfer via proton
exchange between solutes and the surrounding water molecules. It enables us to detect low concentration molecules with
amide, amine and hydroxyl groups. Amide proton transfer (APT) imaging is a specific type of CEST imaging which probes
mobile proteins and peptides. APT is considered to be the most feasible CEST imaging, and has been successfully applied to
brain tumor imaging. Previous studies have shown that APT can help preoperatively estimate the histological grade of gliomas
based on higher APT signal in high grade tumors than in low grade ones. Moreover, it is reportedly useful in discriminating
post-treatment tumor recurrence from treatment-related changes. A hypothetical theory of the high APT signal in malignant
brain gliomas is higher intracellular protein/peptide content due to higher proliferative activity. However, underlying
mechanisms of APT contrast in tumors are not fully understood. It seems obvious that extracellular proteins/peptides can also
contribute to APT signals. Indeed, effects of hemorrhage and edema associated with tumors on APT imaging have never been
carefully evaluated. In this presentation, I will discuss about the clinical usefulness and the limitations of CEST/APT imaging
in evaluating brain tumors.
Keywords : Chemical exchange saturation transfer, Amide proton transfer, Brain tumor
ICMRI2017
March 23-25, 2017 | Grand Hilton Hotel, Seoul, Korea
Asian Forum Session 2: CEST/MT
SY21-5
Amide Proton Transfer Imaging in Stroke: Protocol Optimization and Potential Clinical
Applications
Ji Eun Park
Radiology, Asan Medical Center, Seoul, Korea
Molecular imaging using endogenous molecules has always generated interest because the methodology does not have the
adverse effects of gadolinium (Gd) contrast agents and has clinical benefits for pediatric patients or patients with a
contraindication to an exogenous contrast agent. Amide proton transfer (APT) imaging is gaining attention as a relatively new
in vivo molecular imaging technique that has higher sensitivity and spatial resolution than magnetic resonance spectroscopy
imaging. APT imaging is a subset of the chemical exchange saturation transfer (CEST) mechanism, which can offer unique
image contrast by selectively saturating protons in target molecules exchanged with protons in bulk water.
APT imaging can reflect tissue physic-chemical properties. In patients with acute stroke, APT produces negative contrast
followed by a rather simplified equation (reference 1):
APTR = k[amide proton]/2[H20]R1w * (1-exponential [-R1w * saturation time])
So far, first and only clinical study of APT imaging in actual stroke patients was published in 2013 (reference 2). In 10 patients
with acute anterior or posterior infarctions, APT imaging on a 3T MRI scanner was performed, and reduced APT asymmetry
was noted compared to the contralateral side (P = 0.003). However, the protocol was based on gradient-echo sequence and
needed to be further optimized. Recently, a 3-dimensional turbo spin-echo (TSE) imaging was implemented with APT
imaging, enabled a long duration for off-resonance saturation RF pulse and resulted in high contrast.
In this lecture, I will introduce steps for optimizing protocol of APT imaging in stroke patients, which was validated in rat
stroke model on 3T machine. Also, I will provide illustrative cases of APT imaging in patients with stroke. Also, potential
clinical applications of APT imaging as integrated approach for stroke imaging will be discussed.
References:
1. Zhou JY, Payen JF, Wilson DA, Traystman RJ, van Zijl PCM. Using the amide proton signals of intracellular proteins and
peptides to detect pH effects in MRI. Nature Medicine 2003;9:1085-1090
2. Tietze A, Blicher J, Mikkelsen IK, Ostergaard L, Strother MK, Smith SA, et al. Assessment of ischemic penumbra in
patients with hyperacute stroke using amide proton transfer (APT) chemical exchange saturation transfer (CEST) MRI. NMR
Biomed 2014;27:163-174
3. Keupp J, Baltes C, Harvey P, J. VdB. Parallel RF transmission based MRI technique for highly sensitive detection of amide
proton transfer in the human brain at 3T. In: Proc 19th Annual Meeting ISMRM 2011;Montreal.
ICMRI2017
March 23-25, 2017 | Grand Hilton Hotel, Seoul, Korea
Fig 1.
Legend : A 46 year old patient with acute stroke 4 days ago. MR angiography shows occlusion of right middle cerebral artery
(MCA). Note that reduced APT asymmetry is observed in right MCA territory slightly larger than restricted diffusion regions.
Keywords : Amide proton transfer, PH weighted imaging, Stroke
ICMRI2017
March 23-25, 2017 | Grand Hilton Hotel, Seoul, Korea
Asian Forum Session 2: CEST/MT
SY21-6
Magnetic Resonance GluCEST Imaging
Renhua Wu, Zhuozhi Dai, Yanzi Chen
Medical Imaging, Shantou University Medical College, Shantou, China
Chemical exchange saturation transfer (CEST) imaging is a variant of magnetization transfer (MT) MRI contrast mechanism
that probes the chemical exchange between dilute labile protons and bulk water. CEST can indirectly detect the metabolite
content on the basis of exchangeable protons that exchange with bulk water and provides better spatial and temporal resolutions
compared with 1H magnetic resonance spectroscopy. The CEST technique has previously been used to map pH changes based
on amide proton (–NH) exchange with bulk water, the protein content in the brain, glycogen changes in the liver, and
proteoglycans in the knee cartilage. Some small metabolites such as glutamate (Glu), myoinositol (MI), and creatine (Cr) were
also imaged using CEST.
Since the amount of protons in tissue metabolites (like Glu) is much smaller than that of water protons, when ¹H-MRS is
applied to living tissue to obtain noninvasive biochemical information on small and mobile metabolites (for example, the
concentration of Glu) and physiological parameters, it is strongly limited in terms of signal-to-noise ratio (SNR), spatial
resolution and scanning time in vivo.
Recent studies showed that at the asymmetric magnetization transfer ratio (MTRasymmetry) of 3 ppm, we could find a large
fraction of Glu signal, with the relative amount depending on the saturation power used. We used 3 ppm as the GluCEST
resonance saturation frequency, and our phantom studies at 7.0T demonstrated a similar result that the GluCEST effect depends
on different concentrations. In brain, in-vivo human GluCEST maps showed a similar distribution pattern of Glu. Early
applications of GluCEST to animal models of Alzheimer’s disease have been reported. Detecting the changes in Glu
concentration by GluCEST is becoming increasingly practicable.
Though GluCEST has begun to be translated from experimental studies to patient studies, it is still a relatively immature
imaging technique so far, and there are lots of problems remained, like the phenomenon of intermediate to fast exchange (κ
Δω) which mediates the maximum of asymmetry plot occurred at 1.2 ppm, but not 3.00 ppm at pH 7, and the unified
mechanism of correcting the B1 and B0 map is still indeterminated. Despite of these limitations, based on abundant theories
and data from preclinical or clinical studies, GluCEST has possessed its glamour of mapping relative changes of Glu
concentration.
Keywords : Magnetic resonance, CEST, Glutamate