Real-Time fMRI Brain Mapping in Animals.

Dynamic fMRI responses vary largely according to the physiological conditions of animals either under anesthesia or in awake states. We developed a real-time fMRI platform to guide experimenters to monitor fMRI responses instantaneously during acquisition, which can be used to modify the physiology of animals to achieve desired hemodynamic responses in animal brains. The real-time fMRI set-up is based on a 14.1T preclinical MRI system, enabling the real-time mapping of dynamic fMRI responses in the primary forepaw somatosensory cortex (FP-S1) of anesthetized rats. Instead of a retrospective analysis to investigate confounding sources leading to the variability of fMRI signals, the real-time fMRI platform provides a more effective scheme to identify dynamic fMRI responses using customized macro-functions and a common neuroimage analysis software in the MRI system. Also, it provides immediate troubleshooting feasibility and a real-time biofeedback stimulation paradigm for brain functional studies in animals.

SAR comparison between CASL and pCASL at high magnetic field and evaluation of the benefit of a dedicated labeling coil.

PURPOSE: To investigate the heating induced by (pseudo)-continuous arterial spin labeling ((p)CASL) sequences in vivo at 9.4T and to evaluate the benefit of a dedicated labeling coil. METHODS: Temperature was measured continuously in the brain, neck, and rectum of 9 rats with fiber-optic temperature probes while running pCASL-EPI and CASL-EPI sequences, with labeling B1 amplitudes (B1ave ) of 3, 5, and 7 µT and using a dedicated labeling RF coil or a volume coil. From the temperature time courses, the corresponding specific absorption rate (SAR) was computed. A trade-off between SAR and labeling quality was determined based on measured inversion efficiencies. RESULTS: ASL experiments with standard parameters (B1ave = 5 µT, Tacq = 4 min, labeling with volume coil) lead to a brain temperature increase due to RF of 0.72 ± 0.46 K for pCASL and 0.25 ± 0.17 K for CASL. Using a dedicated labeling coil reduced the RF-induced SAR by a factor of 10 in the brain and a factor of 2 in the neck. Besides SAR due to RF, heat from the coil decoupling circuits produced significant temperature increases. When labeling with a dedicated coil, this mechanism was the dominant source of brain heating. At equivalent RF-SAR, CASL provided slightly superior label efficiency to pCASL and is therefore the preferred sequence when an ASL coil is available. CONCLUSION: B1ave = 4-5 µT provided a good compromise between label efficiency and SAR, both for pCASL and CASL. The sensitivity of animals to heating should be taken into account when optimizing preclinical ASL protocols and may require reducing scan duration or lowering B1ave .

Interpulse phase corrections for unbalanced pseudo-continuous arterial spin labeling at high magnetic field.

PURPOSE: To evaluate a prescan-based radiofrequency phase-correction strategy for unbalanced pseudo-continuous arterial spin labeling (pCASL) at 9.4 T in vivo and to test its robustness toward suboptimal shim conditions. METHODS: Label and control interpulse phases were optimized separately by means of two prescans in rats. The mean perfusion as well as the interhemispherical symmetry were measured for several phase combinations (optimized versus theoretical phases) to evaluate the correction quality. Interpulse phases were also optimized under degraded shim conditions (i.e., up to four times the study shim values) to test the strategy's robustness. RESULTS: For all tested shim conditions, the full arterial spin labeling (ASL) signal could be restored. Without any correction, the relative ASL signal was 1.4 ± 1.7%. It increased to 3.6 ± 1.4% with an optimized label phase and to 5.3 ± 1.2% with optimized label and control phases. Moreover, asymmetry between brain hemispheres, which could be as high as 100% without phase optimization, was dramatically reduced to 1 ± 3% when applying optimized label and control phases. CONCLUSIONS: Pseudo-continuous ASL at high magnetic field is very sensitive to shim conditions. Label and control radiofrequency phase optimization based on prescans robustly maximizes the ASL signal obtained with unbalanced pCASL and minimizes the asymmetry between hemispheres. Magn Reson Med 79:1314-1324, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Impact of tissue T1 on perfusion measurement with arterial spin labeling.

PURPOSE: Arterial spin labeling (ASL) may provide quantitative maps of cerebral blood flow (CBF). Because labeled water exchanges with tissue water, this study evaluates the influence of tissue T1 on CBF quantification using ASL. METHODS: To locally modify T1 , a low dose of manganese (Mn) was intracerebrally injected in one hemisphere of 19 rats (cortex or striatum). Tissue T1 and CBF were mapped using inversion recovery and continuous ASL experiments at 4.7T. RESULTS: Mn reduced the tissue T1 by more than 30% but had little impact on other tissue properties as assessed via dynamic susceptibility and diffusion MRI. Using a single-compartment model, the use of a single tissue T1 value yielded a mean relative ipsilateral (Mn-injected) to contralateral (noninjected) CBF difference of -34% in cortex and -22% in striatum tissue. With a T1 map, these values became -7% and +8%, respectively. CONCLUSION: A low dose of Mn reduces the tissue T1 without modifying CBF. Heterogeneous T1 impacts the ASL estimate of CBF in a region-dependent way. In animals, and when T1 modifications exceed the accuracy with which the tissue T1 can be determined, an estimate of tissue T1 should be obtained when quantifying CBF with an ASL technique. Magn Reson Med 77:1656-1664, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

High-resolution ZTE imaging of human teeth.

MRI with zero echo time (ZTE) is achieved by 3D radial centre-out encoding and hard-pulse RF excitation while the projection gradient is already on. Targeting short-T(2) samples, the efficient, robust and silent ZTE approach was implemented for high-bandwidth high-resolution imaging requiring particularly rapid transmit-receive switching and algebraic image reconstruction. The ZTE technique was applied to image extracted human teeth at 11.7T field strength, yielding detailed depictions with very good delineation of the mineralised dentine and enamel layers. ZTE results are compared with UTE (ultra-short echo time) MRI and micro-computed tomography (µCT), revealing significant differences in SNR and CNR yields. Compared to µCT, ZTE MRI appears to be less susceptible to artefacts caused by dental fillings and to offer superior sensitivity for the detection of early demineralisation and caries lesions.

[Magnetic resonance tomography: potentials of molecular imaging]. / Magnet-Resonanz-Tomographie: Möglichkeiten der molekularen Bildgebung.

Molecular imaging is "the in-vivo characterization and measurement of biological processes at the cellular and molecular level" and allows the imaging of molecular abnormalities associated with diseases long before morphological changes can be detected. At present, the use of magnetic resonance imaging (MRI) for molecular and cellular imaging is rapidly increasing. MRI is a very attractive candidate, since current MRI protocols already provide anatomic, functional, and biochemical information of excellent image quality and with high spatial resolution. Combining this high spatial resolution/high contrast imaging modality with specific MRI contrast imaging agents for molecular imaging is currently the focus of research in many laboratories worldwide. This paper summarizes the rationale for molecular MRI imaging and describes the basic features of modern molecular imaging strategies with MRI. Finally, a special focus is given to the growing field of applications, e.g., stem cell imaging, imaging of apoptosis, plaques, and other biological targets of interest.

Investigation of the microstructure of the isolated rat heart: a comparison between T*2- and diffusion-weighted MRI.

Myocardial fiber structure can be determined with diffusion-weighted (DW) MRI as well as with high-resolution T*(2) imaging. The purpose of the present study was twofold: to provide a more quantitative description of T*(2)-based myocardial fiber contrast, and to compare the T*(2)-based fiber structure with high-resolution (78 microm in-plane, 1-mm slice thickness) DW images of the isolated rat heart at 11.75 T. This study demonstrates that the static dephasing regime is responsible for visualization of myocardial microstructure, and that the dynamic dephasing regime can be neglected. In comparison with DW experiments, T*(2) mapping and DW images yield almost equivalent information on myocardial fiber structure.

Time-resolved flow measurement in the isolated rat heart: characterization of left coronary artery stenosis.

The investigation of flow behavior in coronary arteries is of great importance for an understanding of heart failure and heart regulation mechanisms. The purpose of the present study was to demonstrate that flow velocity can be quantified in the coronary arteries of the isolated rat heart with high-resolution phase contrast MRI. A phase contrast cine-FLASH imaging sequence was used for flow quantification with an in-plane resolution of 70 microm and a slice thickness of 500 microm. With time-resolved measurements, coronary flow over the heart cycle was analyzed. Furthermore, the flow behavior in coronary stenosis was investigated and the degree of stenosis was quantified with MR phase contrast imaging. To achieve the required spatial resolution and a satisfactory signal-to-noise ratio, the experiments were performed at 11.75 T.

Chronic coronary artery stenosis induces impaired function of remote myocardium: MRI and spectroscopy study in rat.

Our purpose was to study morphological, functional, and metabolic changes induced by chronic ischemia in myocardium supplied by the stenotic vessel and in the remote area by MR techniques. A new technique of image fusion is proposed for analysis of coronary artery stenosis involving coronary MR angiography and spectroscopic imaging. Cine-MRI was performed 2 wk after induction of coronary stenosis. Global heart function and regional wall thickening were determined in 11 Wistar rats with stenosis and compared with 7 control rats. Two weeks after stenosis was induced, spin-labeling MRI for measurement of perfusion was performed in 14 isolated hearts. In eight isolated hearts with coronary stenosis, MR spectroscopy was performed, followed by angiography. 31P metabolite maps were fused with three-dimensional coronary angiograms. Induction of stenosis led to reduced segmental wall thickening (control: 75 +/- 9%, ischemic region: 9 +/- 3%, P < 0.05 vs. control) but also to impaired function of the remote region and lower cardiac output. Perfusion was reduced by 74.9 +/- 4.0% within ischemic segments compared with a septal control region. The phosphocreatine (PCr)/ATP ratio as a marker of ischemia was reduced in the region associated with stenosis (1.09 +/- 0.09) compared with remote (1.27 +/- 0.08) and control hearts (1.43 +/- 0.08; P < 0.05). The histological fraction of fibrosis within the ischemic region (12.8 +/- 1.4%) correlated to ATP signal reduction from remote to the ischemic region (r = 0.71, P < 0.05), but not to reduced wall thickening. Coronary narrowing caused declining function accompanied by diminished PCr/ATP, indicating impaired energy metabolism. Neither decline of function nor PCr signal decline correlated to fraction of fibrosis in histology. In contrast, reduction of ATP correlated to fibrosis and therefore to loss of viability. Impaired function within the ischemic region is associated with decreased PCr. Function of the remote region was affected as well. The fusion of PCr metabolite maps and the coronary angiogram may help to assess coronary morphology and resulting metabolic changes simultaneously.

NMR-microscopy with TrueFISP at 11.75T.

The purpose of this paper is to demonstrate that a fully balanced gradient echo technique (TrueFISP) can be used for microscopic experiments at high static magnetic field strengths. TrueFISP experiments were successfully performed on homogeneous and inhomogeneous objects at 11.75T. High-resolution TrueFISP images were obtained from phantoms, plants, formalin-fixed samples, and from an isolated beating rat heart with an in-plane resolution of 78 micro m and a slice thickness of 500 micro m. The signal-to-noise ratio (SNR) gain of TrueFISP compared to conventional gradient echo or spin echo sequences will allow faster acquisition times or an improvement in spatial resolution for microscopic experiments.

Visualization of myocardial microstructure using high-resolution T*2 imaging at high magnetic field.

The analysis of myocardial microstructure in vivo is important for the determination of myocardial contractility and function. The purpose of the present study was to demonstrate that high-resolution T*2 imaging has the potential to visualize the microstructure of beating, isolated rat hearts. To perform T*2 imaging, a multiple gradient-echo sequence was implemented on an 11.75 Tesla microscopy system. An in-plane resolution of 78 microm and a slice thickness of 250 microm were achieved in 24 min. In comparison to histological sections, the T*2 maps showed an excellent spatial correspondence to the myocardial fiber structure. To demonstrate the utility of this technique, morphologic alterations in myocardial microstructure were investigated in hearts with chronic myocardial infarction. Scar tissue and the extent of the infarcted region were clearly visualized and quantified using high-resolution T*2 imaging.