An overview of CEST MRI for non-MR physicists.

The search for novel image contrasts has been a major driving force in the magnetic resonance (MR) research community, in order to gain further information on the body's physiological and pathological conditions.Chemical exchange saturation transfer (CEST) is a novel MR technique that enables imaging certain compounds at concentrations that are too low to impact the contrast of standard MR imaging and too low to directly be detected in MRS at typical water imaging resolution. For this to be possible, the target compound must be capable of exchanging protons with the surrounding water molecules. This property can be exploited to cause a continuous buildup of magnetic saturation of water, leading to greatly enhanced sensitivity.The goal of the present review is to introduce the basic principles of CEST imaging to the general molecular imaging community. Special focus has been given to the comparison of state-of-the-art CEST methods reported in the literature with their positron emission tomography (PET) counterparts.

Age- and Level-Dependence of Fatty Infiltration in Lumbar Paravertebral Muscles of Healthy Volunteers.

BACKGROUND AND PURPOSE: Normative age-related decline in paravertebral muscle quality is important for reference to disease and risk identification in patients. We aimed to establish age- and vertebral level-dependence of paravertebral (multifidus and erector spinae) muscle volume and fat content in healthy adult volunteers. MATERIALS AND METHODS: In this prospective study multifidus and erector spinae fat signal fraction and volume at lumbar levels L1-L5 were measured in 80 healthy volunteers (10 women and men per decade, 20-62 years of age) by 2-point Dixon 3T MR imaging. ANOVA with post hoc Bonferroni correction compared fat signal fraction and volume among subgroups. Pearson and Spearman analysis were used for correlations (P < .05). RESULTS: Fat signal fraction was higher in women (17.8% ± 10.7%) than men (14.7% ± 7.8%; P < .001) and increased with age. Multifidus and erector spinae volume was lower in women (565.4 ± 83.8 cm(3)) than in men (811.6 ± 98.9 cm(3); P < .001) and was age-independent. No differences in fat signal fraction were shown between the right and left paravertebral muscles or among the L1, L2, and L3 lumbar levels. The fat signal fraction was highest at L5 (women, 31.9% ± 9.3%; men, 25.7% ± 8.0%; P < .001). The fat signal fraction at L4 correlated best with total lumbar fat signal fraction (women, r = 0.95; men, r = 0.92, P < .001). Total fat signal fraction was higher in the multifidus compared with erector spinae muscles at L1-L4 for both sexes (P < .001). CONCLUSIONS: Lumbar paravertebral muscle fat content increases with aging, independent of volume, in healthy volunteers 20-62 years of age. Women, low lumbar levels, and the multifidus muscle are most affected. Further study examining younger and older subjects and the functional impact of fatty infiltrated paravertebral muscles are warranted.

Bisphosphonate-induced osteonecrosis of the jaw: comparison of disease extent on contrast-enhanced MR imaging, [18F] fluoride PET/CT, and conebeam CT imaging.

BACKGROUND AND PURPOSE: Imaging of bisphosphonate-induced osteonecrosis of the jaw is essential for surgical planning. We compared the extent of BONJ on contrast-enhanced MR imaging, [(18)F] fluoride PET/CT, and panoramic views derived from standard conebeam CT with clinical pre- and intraoperative examinations. MATERIALS AND METHODS: Between February 2011 and January 2012, ten subjects with written informed consent (9 women; mean, 69.6 years; range, 53-88 years) were included in this prospective ethics-board-approved study. Patients underwent CEMR imaging, [(18)F] fluoride PET/CT, and CBCT and were clinically examined pre- and intraoperatively. Surgery was performed, and BONJ was histologically confirmed in 9 patients. Location and extent of BONJ on different modalities/examinations were graphically compared (0 = no pathologic finding, 1 = smallest, 5 = largest extent of BONJ). Rank tests were used to assess overall and paired differences of ratings in 9 patients. A P value <.05 was considered statistically significant. RESULTS: Significant differences in BONJ extent among different modalities and examinations were found (P < .001). The highest median rank was seen in PET/CT (4 ± 1.12) and CEMR imaging (4 ± 1.01), followed by intraoperative examinations (3 ± 0.71), CBCT (2 ± 0.33), and preoperative examinations (1 ± 0). No significant differences were found between PET/CT and CEMR imaging (P = .23), except when comparing PET/CT to either CBCT, pre- and intraoperative examinations (all P < .05). Preoperative examinations showed significantly less extensive disease than all other modalities/examinations (all P < .05). CONCLUSIONS: [(18)F] fluoride PET/CT and CEMR imaging revealed more extensive involvement of BONJ compared with panoramic views from CBCT and clinical examinations.

Detection of coronary artery disease by magnetic resonance myocardial perfusion imaging with various contrast medium doses: first European multi-centre experience.

AIMS: Magnetic resonance (MR) first-pass myocardial perfusion imaging during hyperaemia detects coronary artery stenoses in humans with test sensitivity depending on contrast medium (CM)-induced signal change in myocardium. In this prospective multi-centre study, the effect of CM dose on myocardial signal change and on diagnostic performance was evaluated using a stress-only approach. METHODS AND RESULTS: Ninety-four patients with known or suspected coronary artery disease (CAD) were randomised to 0.05,0.10, or 0.15 mmol/kg body weight of an extravascular CM (Gd-DTPA) and X-ray coronary angiography was performed within 30 days prior/after the MR examination. A multi-slice MR technique with identical hardware and software in all centres was used during hyperaemia (adenosine 0.14 mg/kg/min) to monitor myocardial CM wash-in kinetics and data were analysed semi-automatically in a core laboratory. Protocol violations resulted in 80 complete studies with CAD (defined as > or =1 vessel with diameter stenosis > or =50% on quantitative coronary angiography) present in 19/29, 13/24, and 20/27 patients for doses 1, 2, and 3, respectively. In normal myocardium, the upslope increased with CM dose (overall-p<0.0001, ANOVA). For CAD detection the area under the receiver operator characteristics curve for subendocardial data (3 slices with quality score<4 representing 86% of cases) was 0.91+/-0.07 and 0.86+/-0.08 for doses 2 and 3, respectively, and was lower for dose 1 (0.53+/-0.13, p<0.01 and p<0.02 vs. doses 2 and 3, respectively). Corresponding sensitivities/specificities (95% confidence intervals) for pooled doses 2/3 were 93% (77-99%; ns vs. dose 1) and 75% (48-92%;p<0.05 vs. dose 1), respectively. CONCLUSIONS: With increasing doses of CM, a higher signal response in the myocardium was achieved and consequently this stress-only protocol, with CM doses of 0.10-0.15 mmol/kg combined with a semi-automatic analysis, yielded a high diagnostic performance for the detection of CAD.

Magnetic resonance myocardial first-pass perfusion imaging: parameter optimization for signal response and cardiac coverage.

Fast imaging techniques allow monitoring of contrast medium (CM) first-pass kinetics in a multislice mode. Employing shorter recovery times improves cardiac coverage during first-pass conditions, but potentially flattens signal response in the myocardium. The aim of this study was therefore to compare in patients with suspected coronary artery disease (CAD) two echo-planar imaging strategies yielding either extended cardiac coverage or optimized myocardial signal response (protocol A/B, six/four slices; preparation pulse, 60 degrees /90 degrees; delay time, 10/120 msec; readout flip angle, 10 degrees /50 degrees; respectively). In phantoms and myocardium of normal volunteers (N= 10) the CM-induced signal increase was 2.5-3 times higher with protocol B (P < 0.005) than with protocol A. For the detection of individually diseased coronary arteries (> or =1 stenosis with > or =50% diameter reduction on quantitative coronary angiography (QCA)), receiver-operator characteristics of protocol B (signal upslope in 32 sectors/heart) yielded a sensitivity/specificity of 82%/73%, which was superior to protocol A (P < 0.05, N= 14). For the overall detection of CAD, the sensitivity/specificity of protocol B was 85%/81%. An adequate signal response in the myocardium is crucial for a reliable detection of perfusion deficits during first-pass conditions. The presented protocol B detects CAD with a sensitivity and specificity similar to scintigraphic techniques.

Assessment of myocardial perfusion in coronary artery disease by magnetic resonance: a comparison with positron emission tomography and coronary angiography.

BACKGROUND: Monitoring contrast medium wash-in kinetics in hyperemic myocardium by magnetic resonance (MR) allows for the detection of stenosed coronary arteries. In this prospective study, the quality of a multislice MR approach with respect to the detection and sizing of compromised myocardium was determined and compared with positron emission tomography (PET) and quantitative coronary angiography. METHODS AND RESULTS: A total of 48 patients and healthy subjects were studied by MR using a multislice hybrid echo-planar pulse sequence for monitoring the myocardial first pass kinetics of gadolinium-diethylenetriamine pentaacetic acid bismethylamide (Omniscan; 0.1 mmol/kg injected at 3 mL/s IV) during hyperemia (dipyridamole 0.56 mg/kg). Signal intensity upslope as a measure of myocardial perfusion was calculated in 32 sectors per heart from pixelwise parametric maps in the subendocardial layer and for full wall thickness. Before coronary angiography, coronary flow reserve (hyperemia induced by dipyridamole 0.56 mg/kg) was determined in corresponding sectors by (13)N-ammonia PET. Receiver-operator characteristic analysis of subendocardial upslope data revealed a sensitivity and specificity of 91% and 94%, respectively, for the detection of coronary artery disease as defined by PET (mean coronary flow reserve minus 2SD of controls) and a sensitivity and specificity of 87% and 85%, respectively, in comparison with quantitative coronary angiography (diameter stenosis >/=50%). The number of pathological sectors per patient on PET and MR studies correlated linearly (slope, 0.94; r=0.76; P<0.0001). CONCLUSIONS: The presented MR approach reliably identifies patients with coronary artery stenoses and provides information on the amount of compromised myocardium, even when perfusion abnormalities are confined to the subendocardial layer. This modality may qualify for its clinical application in the management of coronary artery disease.

3D contrast-enhanced MR angiography of the run-off vessels: value of image subtraction.

The diagnostic gain associated with image subtractions was assessed regarding contrast-enhanced 3D magnetic resonance angiography (MRA) image sets of the pelvic and lower extremity arteries. The MRA strategy combined a dedicated vascular coil with a single injection, two-station protocol. Voxel-by-voxel signal intensity subtraction was performed on MRA image sets obtained before and during dynamic infusion of a para-magnetic contrast agent. Non-subtracted and subtracted MRA image sets were assessed for the presence of occlusive (four grades) disease, using DSA as the standard of reference. In addition, SNR and CNR were recorded for each vascular segment on both the non-subtracted and subtracted images. While CNR values of subtracted images exceeded those of non-subtracted images (P < 0.05), there was no difference in diagnostic performance. For the detection of hemodynamically significant disease, non-subtracted and subtracted MRA provided overall sensitivity and specificity of 90.2%/90.3% and 95.1%/95.6%, respectively. Concordance between non-subtracted and subtracted MRA was excellent (Kappa = 0.86).

TE-switched double-contrast enhanced visualization of vascular system and instruments for MR-guided interventions.

A visualization principle for MR-guided vascular interventions based on the concerted use of two contrast agents is introduced. The first contrast agent, consisting of small paramagnetic iron oxide particles, was administered intravenously to shorten T(1), and even more so T *(2), of the blood for extended time periods. The second agent, a monomeric gadolinium complex, was added to a solution in an interventional device, such as a percutaneous-transluminal-angioplasty (PTA) balloon, to reduce T(1) with only minor additional effects on T *(2). With appropriate T(1)- and T *(2)-weighting the vascular tree (TE <3 ms) and the device (TE > or =8 ms) could be selectively imaged (TR <20 ms). Potentially, both images could be simultaneously updated in the subsecond range. Whereas a visualization of thin structures like guidewires was found to require pulse-sequence optimization, a successful visualization of a PTA balloon in a swine aorta in vivo was possible with standard sequences.

Ligating clips for three-dimensional MR angiography at 1.5 T: in vitro evaluation.

Artifact size on three-dimensional (3D) magnetic resonance (MR) angiograms and safety of various vascular clips (15 titanium and three absorbable polydioxanone clips) were assessed. All evaluated clips were completely safe. Biodegradable clips rendered no artifacts; titanium clips were associated with susceptibility effects. Artifact size was dependent on clip size, clip orientation, echo time, and degree of k-space coverage. In the presence of titanium vascular clips, fast 3D MR angiography should be performed with the shortest echo time and full k-space coverage.

Sensitivity improvement and new acquisition scheme of heteronuclear active-coupling-pattern-tilting spectroscopy.

A simplified phase-cycling scheme for heteronuclear active-coupling-pattern tilting (ACT) spectroscopy is presented. It is demonstrated that the theoretically expected twofold sensitivity gain over earlier implementations can be experimentally realized. A further intensity increase by a factor of 2 is obtained with standard sensitivity-enhancement pulse-sequence elements. The HSQC-HECADE sequence presented is designed for an accurate determination of heteronuclear one-bond and, with subsequent I-spin isotropic mixing, long-range coupling constants. As an exemplary application, the determination of the (3)J(N,Hbeta) coupling constants in a peptide at natural isotope abundance is demonstrated. Additionally, a new polarization-transfer step for the long-range HSQC-HECADE experiment is proposed which avoids a fixed delay tuned to a specific coupling-constant value. Thus, the long-range correlation experiment does not require prior knowledge of the coupling constants to be measured and yields more uniform cross-peak intensity for a broad range of active coupling constants.

Vascular stents as RF antennas for intravascular MR guidance and imaging.

Stent deployment is used to improve the immediate and long-term results of vascular interventions in various vascular sites. X-ray angiography as an imaging modality is often limited in providing an accurate assessment with regard to vessel size, plaque calcification, or stent deployment. In this study, the potential of using the stent endoprothesis as a radiofrequency (RF) receive-only probe for MR guidance and lesion imaging was investigated. Three different principles were developed to visualize stents actively, the first employing the stent as a loop antenna, the second employing the stent in an electrical dipole configuration, and the third employing the stent in a hybrid configuration as a coaxial line antenna. The three configurations resulted in different signal characteristics. Based on two of these antenna configurations, stent deployment devices were built and evaluated in in vitro as well as in vivo sheep experiments. Active stent visualization allows real-time MR guidance through the vessel tree and monitoring of stent deployment. In addition, the stent antenna may become useful for high resolution imaging of the vessel wall. Magn Reson Med 42:738-745, 1999.

Leonticins D-H, five triterpene saponins from Leontice kiangnanensis.

Five new triterpene saponins, leonticins D-H, were isolated from the tubers of Leontice kiangnanensis. Based on a combination of chemical degradation and spectroscopic analysis (negative ion FAB mass spectrometry and 2D NMR experiments), their structures were characterized as 3-O-alpha-L-arabinopyranosyl-caulophyllogenin 28 -O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6-beta-D- glucopyranoside, 3-O-[beta-D-glucopyranosyl -(1-->3)]-[beta-D-glucopyranosyl- (1-->2)]-alpha-L-arabinopyranosyl-oleanolic acid 28-O-alpha-L-rhamnopyranosyl- (1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside, 3-O-[beta-D-glucopyranosyl-(1-->3)]-[beta-D-glucopyranosyl-(1-->2)]-alph a-L -arabinopyranosyl-hederagenin 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D- glucopyranosyl-(1-->6)-beta-D-glucopyranoside, 3-O-beta-D-xylopyranosyl- (1-->3)-beta-D-galactopyranosyl-(1-->4)-beta-D- glucopyranosyl-(-->3)-alpha-L-arabinopyranosyl-echinocystic acid 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D- glucopyranosyl-(1-->6)-beta-D-glucopyranoside, respectively.

Leonticins A-C, three octasaccharide saponins from Leontice kiangnanensis.

Three octasaccharide saponins, leonticins A, B, and C (1-3), were isolated from the tubers of Leontice kiangnanensis. Their structures were elucidated by a combination of chemical degradation and spectral methods including negative FABMS and NMR measurements as 3-O-beta-D-glucopyranosyl (1-->2)-alpha-L-arabinopyranosylhederagenin 28-O-alpha-L-rhamnopyranosyl (1-->4)-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl(1-->4)-alpha-L-rhamnopyranosyl (1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (1), 3-O-[beta-D-xylopyranosyl(1-->3)-beta-D-galactopyranosyl(1-->4)-beta-D- glucopyranosyl (1-->3)][beta-D-glucopyranosyl(1-2)]-alpha-L-arabinopyranosyloleanoli c acid 28-O-alpha-L-rhamnopyranosyl (1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside (2), and 3-O-[beta-D-xylopyranosyl (1-->3)-beta-D-galactopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->3)] [beta-D-glucopyranosyl(1-->2)]-alpha-L-arabinopyranosylechinocystic++ + acid 28-O-alpha-L-rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl- (1-->6)-beta-D-glucopyranoside (3), respectively. The complete assignments of the proton and carbon resonances for 1-3 were achieved based on extensive 2D NMR analysis (DQF-COSY, TOCSY, ROESY, HSQC, and HMBC).

Study of phospholipid structure by 1H, 13C, and 31P dipolar couplings from two-dimensional NMR.

Various motionally averaged 31P-1H, 13C-1H, 1H-1H, and 31P-13C dipolar couplings were measured for natural-abundance and unoriented phosphocholine in the L alpha phase. The couplings were obtained and assigned by a variety of advanced and partly novel two-dimensional solid-state NMR experiments. Whereas 31P-1H and 31P-13C dipolar couplings provide long-range structural constraints, geminal 1H-1H couplings and the signs of 13C-1H couplings are important new elements in a segmental order-tensor analysis of the lipid headgroup and glycerol backbone. The implications of these measured dipolar couplings for the conformational exchange of the lipid headgroup and the bending of the headgroup from the glycerol backbone are discussed. These dipolar couplings are also analyzed semiquantitatively in terms of the segmental order tensor.

Determination of the backbone torsion angle epsilon in nucleic acids.

The multiplet structure of cross peaks in double-quantum-filtered COSY NMR spectra is analysed for those resonances that include passive heteronuclear couplings. Interestingly, the cross peak involving the sugar-ring protons H2' and H3' in nucleic acids display an E. COSY-type appearance exclusively when the backbone torsion angle epsilon (C4'-C3'-O3'-P) adopts a gauche(-) conformation. This observation allows an unambiguous analysis of the conformation around epsilon, without the knowledge of 3JCP coupling constants.