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PET/MRI enables simultaneous in vivo quantification of ?-cell mass and function.

ABSTRACT: Non-invasive imaging of ?-cells represents a desirable preclinical and clinical tool to monitor the change of ?-cell mass and the loss of function during pre-diabetic stages. Although it is widely accepted that manganese (Mn) ions are actively gated by voltage-dependent calcium channels (VDCC) in response to glucose metabolism, little is known on its specificity in vivo for quantification of islet ?-cell function using Mn and magnetic resonance imaging (MRI). On the other hand, glucagon-like-peptide-1 receptor (GLP-1R) represents a validated target for the estimation of ?-cell mass using radiolabeled exendin-4 (Ex4) and positron emission tomography (PET). However, a multiparametric imaging workflow revealing ?-cell mass and function quantitatively is still missing. Methods: We developed a simultaneous PET/MRI protocol to comprehensively quantify in vivo changes in ?-cell mass and function by targeting, respectively, GLP-1R and VDCC coupled with insulin secretion. Differences in the spatial distribution of Mn and radiolabeled Ex4 were monitored overtime in native and transgenic pancreata, characterized by spontaneous pancreatic neuroendocrine tumor development. Follow-up with mass spectrometry imaging (MSI) and autoradiography allowed the ex vivo validation of the specificity of Mn and PET tracer uptake and the detection of endogenous biometals, such as calcium and zinc, throughout the endocrine and exocrine pancreas. Results: Our in vivo data based on a volumetric PET/MRI readout for native pancreata and insulinomas connects uptake of Mn measured at early imaging time points to high non-specific binding by the exocrine tissue, while specific retention was only found 24 h post injection. These results are supported by cross-validation of the spatial distribution of exogenous 55Mn and endogenous 44Ca and 64Zn as well with the specific internalization of the radiolabeled peptide targeting GLP-1R. Conclusion: Simultaneous PET/MR imaging of the pancreas enabled the comprehensive in vivo quantification of ?-cell function and mass using Mn and radiolabeled Ex4. Most important, our data revealed that only late time-point measurements reflect the Mn uptake in the islet ?-cells, while early time points detect non-specific accumulation of Mn in the exocrine pancreas.

SUBMITTER: Michelotti FC

PROVIDER: S-EPMC6929626 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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PET/MRI enables simultaneous <i>in vivo</i> quantification of β-cell mass and function.

Michelotti Filippo C FC Bowden Gregory G Küppers Astrid A Joosten Lieke L Maczewsky Jonas J Nischwitz Volker V Drews Gisela G Maurer Andreas A Gotthardt Martin M Schmid Andreas M AM Pichler Bernd J BJ

Theranostics 20200101 1

Non-invasive imaging of β-cells represents a desirable preclinical and clinical tool to monitor the change of β-cell mass and the loss of function during pre-diabetic stages. Although it is widely accepted that manganese (Mn) ions are actively gated by voltage-dependent calcium channels (VDCC) in response to glucose metabolism, little is known on its specificity <i>in vivo</i> for quantification of islet β-cell function using Mn and magnetic resonance imaging (MRI). On the other hand, glucagon-l ...[more]

PMID: 31903128

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Project description:Respiratory and cardiac motion is the most serious limitation to whole-body PET, resulting in spatial resolution close to 1 cm. Furthermore, motion-induced inconsistencies in the attenuation measurements often lead to significant artifacts in the reconstructed images. Gating can remove motion artifacts at the cost of increased noise. This paper presents an approach to respiratory motion correction using simultaneous PET/MRI to demonstrate initial results in phantoms, rabbits, and nonhuman primates and discusses the prospects for clinical application.Studies with a deformable phantom, a free-breathing primate, and rabbits implanted with radioactive beads were performed with simultaneous PET/MRI. Motion fields were estimated from concurrently acquired tagged MR images using 2 B-spline nonrigid image registration methods and incorporated into a PET list-mode ordered-subsets expectation maximization algorithm. Using the measured motion fields to transform both the emission data and the attenuation data, we could use all the coincidence data to reconstruct any phase of the respiratory cycle. We compared the resulting SNR and the channelized Hotelling observer (CHO) detection signal-to-noise ratio (SNR) in the motion-corrected reconstruction with the results obtained from standard gating and uncorrected studies.Motion correction virtually eliminated motion blur without reducing SNR, yielding images with SNR comparable to those obtained by gating with 5-8 times longer acquisitions in all studies. The CHO study in dynamic phantoms demonstrated a significant improvement (166%-276%) in lesion detection SNR with MRI-based motion correction as compared with gating (P < 0.001). This improvement was 43%-92% for large motion compared with lesion detection without motion correction (P < 0.001). CHO SNR in the rabbit studies confirmed these results.Tagged MRI motion correction in simultaneous PET/MRI significantly improves lesion detection compared with respiratory gating and no motion correction while reducing radiation dose. In vivo primate and rabbit studies confirmed the improvement in PET image quality and provide the rationale for evaluation in simultaneous whole-body PET/MRI clinical studies.

Project description:Noninvasive methods are needed to explore the heterogeneous tumor microenvironment and its modulation by therapy. Hybrid PET/MRI systems are being developed for small-animal and clinical use. The advantage of these integrated systems depends on their ability to provide MR images that are spatially coincident with simultaneously acquired PET images, allowing combined functional MRI and PET studies of intratissue heterogeneity. Although much effort has been devoted to developing this new technology, the issue of quantitative and spatial fidelity of PET images from hybrid PET/MRI systems to the tissues imaged has received little attention. Here, we evaluated the ability of a first-generation, small-animal MRI-compatible PET scanner to accurately depict heterogeneous patterns of radiotracer uptake in tumors.Quantitative imaging characteristics of the MRI-compatible PET (PET/MRI) scanner were evaluated with phantoms using calibration coefficients derived from a mouse-sized linearity phantom. PET performance was compared with a commercial small-animal PET system and autoradiography in tumor-bearing mice. Pixel and structure-based similarity metrics were used to evaluate image concordance among modalities. Feasibility of simultaneous PET/MRI functional imaging of tumors was explored by following (64)Cu-labeled antibody uptake in relation to diffusion MRI using cooccurrence matrix analysis.The PET/MRI scanner showed stable and linear response. Activity concentration recovery values (measured and true activity concentration) calculated for 4-mm-diameter rods within linearity and uniform activity rod phantoms were near unity (0.97 ± 0.06 and 1.03 ± 0.03, respectively). Intratumoral uptake patterns for both (18)F-FDG and a (64)Cu-antibody acquired using the PET/MRI scanner and small-animal PET were highly correlated with autoradiography (r > 0.99) and with each other (r = 0.97 ± 0.01). On the basis of these data, we performed a preliminary study comparing diffusion MRI and radiolabeled antibody uptake patterns over time and visualized movement of antibodies from the vascular space into the tumor mass.The MRI-compatible PET scanner provided tumor images that were quantitatively accurate and spatially concordant with autoradiography and the small-animal PET examination. Cooccurrence matrix approaches enabled effective analysis of multimodal image sets. These observations confirm the ability of the current simultaneous PET/MRI system to provide accurate observations of intratumoral function and serve as a benchmark for future evaluations of hybrid instrumentation.

Project description:ObjectiveSimultaneous PET/MRIs vary in their quantitative PET performance due to inherent differences in the physical systems and differences in the image reconstruction implementation. This variability in quantitative accuracy confounds the ability to meaningfully combine and compare data across scanners. In this work, we define image reconstruction parameters that lead to comparable contrast recovery curves across simultaneous PET/MRI systems.MethodThe NEMA NU-2 image quality phantom was imaged on one GE Signa and on one Siemens mMR PET/MRI scanner. The phantom was imaged at 9.7:1 contrast with standard spheres (diameter 10, 13, 17, 22, 28, 37 mm) and with custom spheres (diameter: 8.5, 11.5, 15, 25, 32.5, 44 mm) using a standardized methodology. Analysis was performed on a 30 min listmode data acquisition and on 6 realizations of 5 min from the listmode data. Images were reconstructed with the manufacturer provided iterative image reconstruction algorithms with and without point spread function (PSF) modeling. For both scanners, a post-reconstruction Gaussian filter of 3-7 mm in steps of 1 mm was applied. Attenuation correction was provided from a scaled computed tomography (CT) image of the phantom registered to the MR-based attenuation images and verified to align on the non-attenuation corrected PET images. For each of these image reconstruction parameter sets, contrast recovery coefficients (CRCs) were determined for the SUVmean, SUVmax and SUVpeak for each sphere. A hybrid metric combining the root-mean-squared discrepancy (RMSD) and the absolute CRC values was used to simultaneously optimize for best match in CRC between the two scanners while simultaneously weighting toward higher resolution reconstructions. The image reconstruction parameter set was identified as the best candidate reconstruction for each vendor for harmonized PET image reconstruction.ResultsThe range of clinically relevant image reconstruction parameters demonstrated widely different quantitative performance across cameras. The best match of CRC curves was obtained at the lowest RMSD values with: for CRCmean, 2 iterations-7 mm filter on the GE Signa and 4 iterations-6 mm filter on the Siemens mMR, for CRCmax, 4 iterations-6 mm filter on the GE Signa, 4 iterations-5 mm filter on the Siemens mMR and for CRCpeak, 4 iterations-7 mm filter with PSF on the GE Signa and 4 iterations-7 mm filter on the Siemens mMR. Over all reconstructions, the RMSD between CRCs was 1.8%, 3.6% and 2.9% for CRC mean, max and peak, respectively. The solution of 2 iterations-3 mm on the GE Signa and 4 iterations-3 mm on Siemens mMR, both with PSF, led to simultaneous harmonization and with high CRC and low RMSD for CRC mean, max and peak with RMSD values of 2.8%, 5.8% and 3.2%, respectively.ConclusionsFor two commercially available PET/MRI scanners, user-selectable parameters that control iterative updates, image smoothing and PSF modeling provide a range of contrast recovery curves that allow harmonization in harmonization strategies of optimal match in CRC or high CRC values. This work demonstrates that nearly identical CRC curves can be obtained on different commercially available scanners by selecting appropriate image reconstruction parameters.

Project description:Background During simultaneous PET/MRI, flexible MRI surface coils that lay on the patient are often omitted from PET attenuation correction processing, leading to quantification bias in PET images. Purpose To identify potential PET image quality improvement by using a recently developed lightweight MRI coil technology for the anterior array (AA) surface coil in both a phantom and in vivo study. Materials and Methods A phantom study and a prospective in vivo study were performed with a PET/CT scanner under three conditions: (a) no MRI surface coil (standard of reference), (b) traditional AA coil, and (c) lightweight AA coil. AA coils were not used in attenuation correction processing to emulate clinical PET/MRI. For the phantom study, PET images were reconstructed with and without time of flight (TOF) to assess quantification accuracy and uniformity. The in vivo study consisted of 10 participants (mean age, 66 years ± 10 [standard deviation]; six men) referred for a PET/CT oncologic examination who had undergone imaging between October 2019 and February 2020. Assessment of image quantification bias (defined as the standard error of the mean values) was conducted by comparing mean liver region of interest standardized uptake values with the no-coil standard of reference. A Wilcoxon signed-rank test was used to establish significance. Results For TOF and non-TOF, respectively, the phantom study revealed a mean PET quantification bias of -9.0% and -8.6% with the traditional AA coil and a mean PET quantification bias of -4.3% and -4.0% with the lightweight AA coil. The coefficients of variation reduced from 4.3% and 6.2% with the traditional AA coil to 2.1% and 2.7% with the lightweight AA coil, which demonstrated a homogeneity benefit from the lightweight coil that was greater with, versus without, TOF reconstruction. For the in vivo study, the mean liver standardized uptake value error was -5.9% with the traditional AA coil (P = .002 vs no coil) and -2.4% with the lightweight AA coil (P = .004 vs no coil). Conclusion The lightweight anterior array coil reduced PET image quantification bias by more than 50% compared with the traditional coil. Using the lightweight coil and performing time of flight-based reconstruction each reduced the variation of error. © RSNA, 2020 Online supplemental material is available for this article.

Project description:BACKGROUND:Subject motion in positron emission tomography (PET) studies leads to image blurring and artifacts; simultaneously acquired magnetic resonance imaging (MRI) data provides a means for motion correction (MC) in integrated PET/MRI scanners. PURPOSE:To assess the effect of realistic head motion and MR-based MC on static [18 F]-fluorodeoxyglucose (FDG) PET images in dementia patients. STUDY TYPE:Observational study. POPULATION:Thirty dementia subjects were recruited. FIELD STRENGTH/SEQUENCE:3T hybrid PET/MR scanner where EPI-based and T1 -weighted sequences were acquired simultaneously with the PET data. ASSESSMENT:Head motion parameters estimated from high temporal resolution MR volumes were used for PET MC. The MR-based MC method was compared to PET frame-based MC methods in which motion parameters were estimated by coregistering 5-minute frames before and after accounting for the attenuation-emission mismatch. The relative changes in standardized uptake value ratios (SUVRs) between the PET volumes processed with the various MC methods, without MC, and the PET volumes with simulated motion were compared in relevant brain regions. STATISTICAL TESTS:The absolute value of the regional SUVR relative change was assessed with pairwise paired t-tests testing at the P?=?0.05 level, comparing the values obtained through different MR-based MC processing methods as well as across different motion groups. The intraregion voxelwise variability of regional SUVRs obtained through different MR-based MC processing methods was also assessed with pairwise paired t-tests testing at the P?=?0.05 level. RESULTS:MC had a greater impact on PET data quantification in subjects with larger amplitude motion (higher than 18% in the medial orbitofrontal cortex) and greater changes were generally observed for the MR-based MC method compared to the frame-based methods. Furthermore, a mean relative change of ?4% was observed after MC even at the group level, suggesting the importance of routinely applying this correction. The intraregion voxelwise variability of regional SUVRs was also decreased using MR-based MC. All comparisons were significant at the P?=?0.05 level. DATA CONCLUSION:Incorporating temporally correlated MR data to account for intraframe motion has a positive impact on the FDG PET image quality and data quantification in dementia patients. LEVEL OF EVIDENCE:3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1288-1296.

Project description:Understanding sources of electromagnetic interference are important in designing any electronic system. This is especially true when combining positron emission tomography (PET) and magnetic resonance imaging (MRI) in a multimodality system as coupling between the subsystems can degrade the performance of either modality. For this reason, eliminating radio frequency (RF) interference and gradient-induced eddy currents have been major challenges in building simultaneous hybrid PET/MRI systems. MRI requires negligible RF interference at the Larmor resonance frequency, while RF interference at almost any frequency may corrupt PET data. Moreover, any scheme that minimizes these interactions would, ideally, not compromise the performance of either subsystem. This paper lays out a plan to resolve these problems. A carbon fiber composite material is found to be a good RF shield at the Larmor frequency (300MHz in this work) while introducing negligible gradient eddy currents. This carbon fiber composite also provides excellent structural support for the PET detector components. Low frequency electromagnetic radiation (81kHz here) from the switching power supplies of the gradient amplifiers was also found to interfere with the PET detector. Placing the PET detector module between two carbon fiber tubes and grounding the inner carbon fiber tube to the PET detector module ground reduced this interference. Further reductions were achieved by adding thin copper (Cu) foil on the outer carbon fiber case and electrically grounding the PET detector module so that all 3 components had a common ground, i.e. with the PET detector in an electrostatic cage. Finally, gradient switching typical in MRI sequences can result in count losses in the particular PET detector design studied. Moreover, the magnitude of this effect depends on the location of the detector within the magnet bore and which MRI gradient is being switched. These findings have a bearing on future designs of PET/MRI systems.

Project description:We propose a novel approach for PET respiratory motion correction using tagged-MRI and simultaneous PET-MRI acquisitions.We use a tagged-MRI acquisition followed by motion tracking in the phase domain to estimate the nonrigid deformation of biological tissues during breathing. In order to accurately estimate motion even in the presence of noise and susceptibility artifacts, we regularize the traditional HARP tracking strategy using a quadratic roughness penalty on neighboring displacement vectors (R-HARP). We then incorporate the motion fields estimated with R-HARP in the system matrix of an MLEM PET reconstruction algorithm formulated both for sinogram and list-mode data representations. This approach allows reconstruction of all detected coincidences in a single image while modeling the effect of motion both in the emission and the attenuation maps. At present, tagged-MRI does not allow estimation of motion in the lungs and our approach is therefore limited to motion correction in soft tissues. Since it is difficult to assess the accuracy of motion correction approaches in vivo, we evaluated the proposed approach in numerical simulations of simultaneous PET-MRI acquisitions using the NCAT phantom. We also assessed its practical feasibility in PET-MRI acquisitions of a small deformable phantom that mimics the complex deformation pattern of a lung that we imaged on a combined PET-MRI brain scanner.Simulations showed that the R-HARP tracking strategy accurately estimated realistic respiratory motion fields for different levels of noise in the tagged-MRI simulation. In simulations of tumors exhibiting increased uptake, contrast estimation was 20% more accurate with motion correction than without. Signal-to-noise ratio (SNR) was more than 100% greater when performing motion-corrected reconstruction which included all counts, compared to when reconstructing only coincidences detected in the first of eight gated frames. These results were confirmed in our proof-of-principle PET-MRI acquisitions, indicating that our motion correction strategy is accurate, practically feasible, and is therefore ready to be tested in vivo.This work shows that PET motion correction using motion fields measured with tagged-MRI in simultaneous PET-MRI acquisitions can be made practical for clinical application and that doing so has the potential to remove motion blur in whole-body PET studies of the torso.

Dataset Information

PET/MRI enables simultaneous in vivo quantification of ?-cell mass and function.

Publications

PET/MRI enables simultaneous <i>in vivo</i> quantification of β-cell mass and function.

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