Extended MRI-based PET motion correction for cardiac PET/MRI.

PURPOSE: A 2D image navigator (iNAV) based 3D whole-heart sequence has been used to perform MRI and PET non-rigid respiratory motion correction for hybrid PET/MRI. However, only the PET data acquired during the acquisition of the 3D whole-heart MRI is corrected for respiratory motion. This study introduces and evaluates an MRI-based respiratory motion correction method of the complete PET data. METHODS: Twelve oncology patients scheduled for an additional cardiac 18F-Fluorodeoxyglucose (18F-FDG) PET/MRI and 15 patients with coronary artery disease (CAD) scheduled for cardiac 18F-Choline (18F-FCH) PET/MRI were included. A 2D iNAV recorded the respiratory motion of the myocardium during the 3D whole-heart coronary MR angiography (CMRA) acquisition (~ 10 min). A respiratory belt was used to record the respiratory motion throughout the entire PET/MRI examination (~ 30-90 min). The simultaneously acquired iNAV and respiratory belt signal were used to divide the acquired PET data into 4 bins. The binning was then extended for the complete respiratory belt signal. Data acquired at each bin was reconstructed and combined using iNAV-based motion fields to create a respiratory motion-corrected PET image. Motion-corrected (MC) and non-motion-corrected (NMC) datasets were compared. Gating was also performed to correct cardiac motion. The SUVmax and TBRmax values were calculated for the myocardial wall or a vulnerable coronary plaque for the 18F-FDG and 18F-FCH datasets, respectively. RESULTS: A pair-wise comparison showed that the SUVmax and TBRmax values of the motion corrected (MC) datasets were significantly higher than those for the non-motion-corrected (NMC) datasets (8.2 ± 1.0 vs 7.5 ± 1.0, p < 0.01 and 1.9 ± 0.2 vs 1.2 ± 0.2, p < 0.01, respectively). In addition, the SUVmax and TBRmax of the motion corrected and gated (MC_G) reconstructions were also higher than that of the non-motion-corrected but gated (NMC_G) datasets, although for the TBRmax this difference was not statistically significant (9.6 ± 1.3 vs 9.1 ± 1.2, p = 0.02 and 2.6 ± 0.3 vs 2.4 ± 0.3, p = 0.16, respectively). The respiratory motion-correction did not lead to a change in the signal to noise ratio. CONCLUSION: The proposed respiratory motion correction method for hybrid PET/MRI improved the image quality of cardiovascular PET scans by increased SUVmax and TBRmax values while maintaining the signal-to-noise ratio. Trial registration METC162043 registered 01/03/2017.

Quantification of carotid plaque composition with a multi-contrast atherosclerosis characterization (MATCH) MRI sequence.

Background and purpose: Carotid atherosclerotic plaques with a large lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and a thin or ruptured fibrous cap are associated with increased stroke risk. Multi-sequence MRI can be used to quantify carotid atherosclerotic plaque composition. Yet, its clinical implementation is hampered by long scan times and image misregistration. Multi-contrast atherosclerosis characterization (MATCH) overcomes these limitations. This study aims to compare the quantification of plaque composition with MATCH and multi-sequence MRI. Methods: MATCH and multi-sequence MRI were used to image 54 carotid arteries of 27 symptomatic patients with ≥2 mm carotid plaque on a 3.0 T MRI scanner. The following sequence parameters for MATCH were used: repetition time/echo time (TR/TE), 10.1/4.35 ms; field of view, 160 mm × 160 mm × 2 mm; matrix size, 256 × 256; acquired in-plane resolution, 0.63 mm2× 0.63 mm2; number of slices, 18; and flip angles, 8°, 5°, and 10°. Multi-sequence MRI (black-blood pre- and post-contrast T1-weighted, time of flight, and magnetization prepared rapid acquisition gradient echo; acquired in-plane resolution: 0.63 mm2 × 0.63 mm2) was acquired according to consensus recommendations, and image quality was scored (5-point scale). The interobserver agreement in plaque composition quantification was assessed by the intraclass correlation coefficient (ICC). The sensitivity and specificity of MATCH in identifying plaque composition were calculated using multi-sequence MRI as a reference standard. Results: A significantly lower image quality of MATCH compared to that of multi-sequence MRI was observed (p < 0.05). The scan time for MATCH was shorter (7 vs. 40 min). Interobserver agreement in quantifying plaque composition on MATCH images was good to excellent (ICC ≥ 0.77) except for the total volume of calcifications and fibrous tissue that showed moderate agreement (ICC ≥ 0.61). The sensitivity and specificity of detecting plaque components on MATCH were ≥89% and ≥91% for IPH, ≥81% and 85% for LRNC, and ≥71% and ≥32% for calcifications, respectively. Overall, good-to-excellent agreement (ICC ≥ 0.76) of quantifying plaque components on MATCH with multi-sequence MRI as the reference standard was observed except for calcifications (ICC = 0.37-0.38) and fibrous tissue (ICC = 0.59-0.70). Discussion and conclusion: MATCH images can be used to quantify plaque components such as LRNC and IPH but not for calcifications. Although MATCH images showed a lower mean image quality score, short scan time and inherent co-registration are significant advantages.

Evaluation of a Dedicated Radiofrequency Carotid PET/MRI Coil.

Carotid radiofrequency coils inside a PET/MRI system can result in PET quantification errors. We compared the performance of a dedicated PET/MRI carotid coil against a coil for MRI-only use. An 18F-fluorodeoxyglucose (18F-FDG) phantom was scanned without and with an MRI-only coil and with the PET/MRI coil. The decay-corrected normalized activity was compared for the different coil configurations. Eighteen patients were scanned with the three coil configurations. The maximal standardized uptake values (SUVmax) and signal-to-noise ratios (SNR) were calculated. Repeated measures ANOVA was performed to assess the differences in SUVmax and SNR between the coil configurations. In the phantom study, the PET/MRI coil demonstrated a slight decrease (<5%), while the MRI-only coil showed a substantial decrease (up to 10%) in normalized activity at the position of coil elements compared to no dedicated coil configuration. In the patient study, the SUVmax values for both no surface coil (3.59 ± 0.15) and PET/MRI coil (3.54 ± 0.15) were significantly higher (p = 0.03 and p = 0.04, respectively) as compared to the MRI-only coil (3.28 ± 0.16). No significant difference was observed between PET/MRI and no surface coil (p = 1.0). The SNR values for both PET/MRI (7.31 ± 0.44) and MRI-only (7.62 ± 0.42) configurations demonstrated significantly higher (p < 0.001) SNR values as compared to the no surface coil (3.78 ± 0.22), while no significant difference was observed in SNR between the PET/MRI and MRI-only coil (p = 1.0). This study demonstrated that the PET/MRI coil can be used for PET imaging without requiring attenuation correction while acquiring high-resolution MR images.

The Use of 18F-FET-PET-MRI in Neuro-Oncology: The Best of Both Worlds-A Narrative Review.

Gliomas are the most frequent primary tumors of the brain. They can be divided into grade II-IV astrocytomas and grade II-III oligodendrogliomas, based on their histomolecular profile. The prognosis and treatment is highly dependent on grade and well-identified prognostic and/or predictive molecular markers. Multi-parametric MRI, including diffusion weighted imaging, perfusion, and MR spectroscopy, showed increasing value in the non-invasive characterization of specific molecular subsets of gliomas. Radiolabeled amino-acid analogues, such as 18F-FET, have also been proven valuable in glioma imaging. These tracers not only contribute in the diagnostic process by detecting areas of dedifferentiation in diffuse gliomas, but this technique is also valuable in the follow-up of gliomas, as it can differentiate pseudo-progression from real tumor progression. Since multi-parametric MRI and 18F-FET PET are complementary imaging techniques, there may be a synergistic role for PET-MRI imaging in the neuro-oncological imaging of primary brain tumors. This could be of value for both primary staging, as well as during treatment and follow-up.

Iron Oxide Nanoparticle Uptake in Mouse Brachiocephalic Artery Atherosclerotic Plaque Quantified by T2-Mapping MRI.

The purpose of our study was to monitor the iron oxide contrast agent uptake in mouse brachiocephalic artery (BCA) atherosclerotic plaques in vivo by quantitative T2-mapping magnetic resonance imaging (MRI). Female ApoE-/- mice (n = 32) on a 15-week Western-type diet developed advanced plaques in the BCA and were injected with ultra-small superparamagnetic iron oxides (USPIOs). Quantitative in vivo MRI at 9.4 T was performed with a Malcolm-Levitt (MLEV) prepared T2-mapping sequence to monitor the nanoparticle uptake in the atherosclerotic plaque. Ex vivo histology and particle electron paramagnetic resonance (pEPR) were used for validation. Longitudinal high-resolution in vivo T2-value maps were acquired with consistent quality. Average T2 values in the plaque decreased from a baseline value of 34.5 ± 0.6 ms to 24.0 ± 0.4 ms one day after injection and partially recovered to an average T2 of 27 ± 0.5 ms after two days. T2 values were inversely related to iron levels in the plaque as determined by ex vivo particle electron paramagnetic resonance (pEPR). We concluded that MRI T2 mapping facilitates a robust quantitative readout for USPIO uptake in atherosclerotic plaques in arteries near the mouse heart.

PET/MRI of atherosclerosis.

Myocardial infarction and stroke are the most prevalent global causes of death. Each year 15 million people worldwide die due to myocardial infarction or stroke. Rupture of a vulnerable atherosclerotic plaque is the main underlying cause of stroke and myocardial infarction. Key features of a vulnerable plaque are inflammation, a large lipid-rich necrotic core (LRNC) with a thin or ruptured overlying fibrous cap, and intraplaque hemorrhage (IPH). Noninvasive imaging of these features could have a role in risk stratification of myocardial infarction and stroke and can potentially be utilized for treatment guidance and monitoring. The recent development of hybrid PET/MRI combining the superior soft tissue contrast of MRI with the opportunity to visualize specific plaque features using various radioactive tracers, paves the way for comprehensive plaque imaging. In this review, the use of hybrid PET/MRI for atherosclerotic plaque imaging in carotid and coronary arteries is discussed. The pros and cons of different hybrid PET/MRI systems are reviewed. The challenges in the development of PET/MRI and potential solutions are described. An overview of PET and MRI acquisition techniques for imaging of atherosclerosis including motion correction is provided, followed by a summary of vessel wall imaging PET/MRI studies in patients with carotid and coronary artery disease. Finally, the future of imaging of atherosclerosis with PET/MRI is discussed.

Small animal cardiovascular MR imaging and spectroscopy.

The use of MR imaging and spectroscopy for studying cardiovascular disease processes in small animals has increased tremendously over the past decade. This is the result of the remarkable advances in MR technologies and the increased availability of genetically modified mice. MR techniques provide a window on the entire timeline of cardiovascular disease development, ranging from subtle early changes in myocardial metabolism that often mark disease onset to severe myocardial dysfunction associated with end-stage heart failure. MR imaging and spectroscopy techniques play an important role in basic cardiovascular research and in cardiovascular disease diagnosis and therapy follow-up. This is due to the broad range of functional, structural and metabolic parameters that can be quantified by MR under in vivo conditions non-invasively. This review describes the spectrum of MR techniques that are employed in small animal cardiovascular disease research and how the technological challenges resulting from the small dimensions of heart and blood vessels as well as high heart and respiratory rates, particularly in mice, are tackled.

Evaluation of iron oxide nanoparticle micelles for magnetic particle imaging (MPI) of thrombosis.

Magnetic particle imaging (MPI) is an emerging medical imaging modality that directly visualizes magnetic particles in a hot-spot like fashion. We recently developed an iron oxide nanoparticle-micelle (ION-Micelle) platform that allows highly sensitive MPI. The goal of this study was to assess the potential of the ION-Micelles for MPI-based detection of thrombi. To this aim, an in vivo carotid artery thrombosis mouse model was employed and ex vivo magnetic particle spectrometer (MPS) measurements of the carotid arteries were performed. In addition, we studied the effect of functionalization of the ION-Micelle nanoplatform with fibrin-binding peptides (FibPeps) with respect to nanoparticle thrombus uptake and hence thrombus detection. In vivo quantitative MR imaging pre- and post-ION-Micelle injection was performed as reference for visualization of ION-micelle uptake. ION-Micelles significantly decreased T2 values in the thrombi with respect to pre-injection T2 values (p < 0.01) and significantly increased ex vivo MPS thrombus signal with respect to the noninjured, contralateral carotid (p < 0.01). Functionalization of the ION-Micelles with the FibPep peptides did not result in an increased MPS thrombus signal with respect to the non-fibrin binding ION-Micelles. The lack of a significant increased thrombus uptake for the FibPep-ION-Micelles indicates that (non-fibrin-specific) entrapment of nanoparticles in the mesh-like thrombi is the key contributor to thrombus nanoparticle uptake. Therefore, (nontargeted) ION-Micelles might be of value for noninvasive MPI-based diagnosis, characterization and treatment monitoring of thrombosis.

T1 ρ mapping for the evaluation of high intensity focused ultrasound tumor treatment.

PURPOSE: This study was aimed to assess the effects of High Intensity Focused Ultrasound (HIFU) thermal ablation on tumor T1ρ . METHODS: In vivo T1ρ measurements of murine tumors at various spin-lock amplitudes (B1 = 0-2000 Hz) were performed before (n = 13), directly after (n = 13) and 3 days (n = 7) after HIFU treatment. T2 maps were obtained from the measurements at B1 = 0 Hz. RESULTS: Average tumor T1ρ distributions at the different experimental time points showed a shift toward lower T1ρ values after HIFU for all spin-lock amplitudes, which became larger with increasing spin-lock amplitude at 3 days after treatment. Statistical analysis confirmed a significant effect of spin-lock amplitude on the average change in T1ρ (ΔT1ρ ) as compared to baseline at 3 days after HIFU. At 3 days after treatment, ΔT1ρ values at B1 above 100 Hz were significantly lower (more negative) than at B1 = 0 Hz (T2 ). CONCLUSION: Significant changes in tumor T1ρ were observed after HIFU treatment. These T1ρ changes were distinctly more pronounced than HIFU-induced changes in T2 . The results indicate that T1ρ imaging is sensitive to HIFU-induced tissue changes and may thus be a suitable MR method for the evaluation of HIFU treatment. Magn Reson Med 73:1593-1601, 2015. © 2014 Wiley Periodicals, Inc.

Spin-lock MR enhances the detection sensitivity of superparamagnetic iron oxide particles.

PURPOSE: To evaluate spin-lock MR for detecting superparamagnetic iron oxides and compare the detection sensitivity of quantitative T1ρ with T2 imaging. METHODS: In vitro experiments were performed to investigate the influence of iron oxide particle size and composition on T1ρ . These comprise T1ρ and T2 measurements (B0 = 1.41T) of agar (2%) with concentration ranges of three different iron oxide nanoparticles (IONs) (Sinerem, Resovist, and ION-Micelle) and microparticles of iron oxide (MPIO). T1ρ dispersion was measured for a range of spin-lock amplitudes (γB1 = 6.5-91 kHz). Under relevant in vivo conditions (B0 = 9.4T; γB1 = 100-1500 Hz), T1ρ and T2 mapping of the liver was performed in seven mice pre- and 24 h postinjection of Sinerem. RESULTS: Addition of iron oxide nanoparticles decreased T1ρ as well as the native T1ρ dispersion of agar, leading to increased contrast at high spin-lock amplitudes. Changes of T1ρ were highly linear with iron concentration and much larger than T2 changes. MPIO did not show this effect. In vivo, a decrease of T1ρ was observed with no clear influence on T1ρ dispersion. CONCLUSION: By suppression of T1ρ dispersion, iron oxide nanoparticles cause enhanced T1ρ contrast compared to T2 . The underlying mechanism appears to be loss of lock. Spin-lock MR is therefore a promising technique for sensitive detection of iron oxide contrast agents.

Quantitative T2 mapping of the mouse heart by segmented MLEV phase-cycled T2 preparation.

PURPOSE: A high-quality, reproducible, multi-slice T2-mapping protocol for the mouse heart is presented. METHODS: A T2-prepared sequence with composite 90° and 180° radiofrequency pulses in a segmented MLEV phase cycling scheme was developed. The T2-mapping protocol was optimized using simulations and evaluated with phantoms. RESULTS: Repeatability for determination of myocardial T2 values was assessed in vivo in n = 5 healthy mice on 2 different days. The average baseline T2 of the left ventricular myocardium was 22.5 ± 1.7 ms. The repeatability coefficient for R2 = 1/T2 for measurements at different days was ΔR2 = 6.3 s(−1). Subsequently, T2 mapping was applied in comparison to late-gadolinium-enhancement (LGE) imaging, to assess 1-day-old ischemia/reperfusion (IR) myocardial injury in n = 8 mice. T2 in the infarcts was significantly higher than in remote tissue, whereas remote tissue was not significantly different from baseline. Infarct sizes based on T2 versus LGE showed strong correlation. To assess the time-course of T2 changes in the infarcts, T2 mapping was performed at day 1, 3, and 7 after IR injury in a separate group of mice (n = 16). T2 was highest at day 3, in agreement with the expected time course of edema formation and resolution after myocardial infarction. CONCLUSION: T2 prepared imaging provides high quality reproducible T2 maps of healthy and diseased mouse myocardium.

Iron oxide nanoparticle-micelles (ION-micelles) for sensitive (molecular) magnetic particle imaging and magnetic resonance imaging.

BACKGROUND: Iron oxide nanoparticles (IONs) are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI) was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI. METHODS AND RESULTS: IONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles). Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS) measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem) and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles) bound to blood clots. CONCLUSIONS: The presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular) MPI and warrants further investigation of the FibPep-ION-Micelle platform for in vivo, non-invasive imaging of fibrin in preclinical disease models of thrombus-related pathologies and atherosclerosis.

Mouse myocardial first-pass perfusion MR imaging.

A first-pass myocardial perfusion sequence for mouse cardiac MRI is presented. A segmented ECG-triggered acquisition combined with parallel imaging acceleration was used to capture the first pass of a Gd-DTPA bolus through the mouse heart with a temporal resolution of 300-400 msec. The method was applied in healthy mice (N = 5) and in mice with permanent occlusion of the left coronary artery (N = 6). Baseline semiquantitative perfusion values of healthy myocardium showed excellent reproducibility. Infarct regions revealed a significant decrease in the semiquantitative myocardial perfusion values (0.05 ± 0.02) compared to remote myocardium (0.20 ± 0.04). Myocardial areas of decreased perfusion correlated well to infarct areas identified on the delayed-enhancement scans. This protocol is a valuable addition to the mouse cardiac MRI toolbox for preclinical studies of ischemic heart disease.