Simultaneous MR-PET Research Articles

Characterization of cortico-meningeal translocator protein expression in multiple sclerosis.

Compartmentalized meningeal inflammation is thought to represent one of the key players in the pathogenesis of cortical demyelination in multiple sclerosis. PET targeting the 18 kDa mitochondrial translocator protein (TSPO) is a molecular-specific approach to quantifying immune cell-mediated density in the cortico-meningeal tissue compartment in vivo. This study aimed to characterize cortical and meningeal TSPO expression in a heterogeneous cohort of multiple sclerosis cases using in vivo simultaneous MR-PET with 11C-PBR28, a second-generation TSPO radioligand, and ex vivo immunohistochemistry. Forty-nine multiple sclerosis patients (21 with secondary progressive and 28 with relapsing-remitting multiple sclerosis) with mixed or high affinity binding for 11C-PBR28 underwent 90-min 11C-PBR28 simultaneous MR-PET. Tracer binding was measured using 60-90 min normalized standardized uptake value ratios sampled at mid-cortical depth and ∼3 mm above the pial surface. Data in multiple sclerosis patients were compared to 21 age-matched healthy controls. To characterize the nature of 11C-PBR28 PET uptake, the meningeal and cortical lesion cellular expression of TSPO was further described in post-mortem brain tissue from 20 cases with secondary progressive multiple sclerosis and five age-matched healthy donors. Relative to healthy controls, patients with multiple sclerosis exhibited abnormally increased TSPO signal in the cortex and meningeal tissue, diffusively in progressive disease and more localized in relapsing-remitting multiple sclerosis. In multiple sclerosis, increased meningeal TSPO levels were associated with increased Expanded Disability Status Scale scores (P = 0.007, by linear regression). Immunohistochemistry, validated using in situ sequencing analysis, revealed increased TSPO expression in the meninges and adjacent subpial cortical lesions of post-mortem secondary progressive multiple sclerosis cases relative to control tissue. In these cases, increased TSPO expression was related to meningeal inflammation. Translocator protein immunostaining was detected on meningeal MHC-class II+ macrophages and cortical-activated MHC-class II+ TMEM119+ microglia. In vivo arterial blood data and neuropathology showed that endothelial binding did not significantly account for increased TSPO cortico-meningeal expression in multiple sclerosis. Our findings support the use of TSPO-PET in multiple sclerosis for imaging in vivo inflammation in the cortico-meningeal brain tissue compartment and provide in vivo evidence implicating meningeal inflammation in the pathogenesis of the disease.

In Vivo And Ex Vivo Characterization Of Meningeal Translocator Protein Expression In Multiple Sclerosis (S9.010)

In Vivo And Ex Vivo Characterization Of Meningeal Translocator Protein Expression In Multiple Sclerosis (S9.010)

CURVED MULTIFORMAT IMAGING OF STRUCTURAL MRI AS A BIOMARKER FOR PROFILING OF VARIOUS DEMENTIA - AN ALGORITHMIC APPROACH WITH MR/PET.

Dementia is one of the most common clinical entities for which neuroimaging is done for diagnosis and characterization of the sub-types. Advanced neuroimaging modalities like MR-PET have added to the armamentarium of the neuroradiologists for the diagnosis of specific types of dementia syndromes. However, advanced molecular imaging is expensive and is not widely available particularly in underdeveloped countries. Structural imaging with MRI in addition to the clinical work up remains the most useful approach to the diagnosis of dementia in our setup. We describe a simple technique of curved multiplanar reconstruction of brain images with the use of a simple reconstruction software which can help in recognition of pattern of atrophy in dementias and thus improve the diagnostic accuracy of structural MRI. Using this approach of pattern recognition, we suggest a simplified algorithm for diagnosis of sub-types of dementia. In our study, we applied this technique for demonstration of pattern of atrophy which correlated with metabolic changes on PET in a variety of dementia cases using simultaneous MR-PET imaging and may act as a low cost and reliable biomarker to profile dementia subtypes. To the best of our knowledge this is the first study to show the utility of curved multiplanar reconstruction in dementias.

A Novel J-Shape Antenna Array for Simultaneous MR-PET or MR-SPECT Imaging.

Simultaneous MR-PET/-SPECT is an emerging technology that capitalises on the invaluable advantages of both modalities, allowing access to numerous sensitive tracers and superior soft-tissue contrast alongside versatile functional imaging capabilities. However, to optimise these capabilities, concurrent acquisitions require the MRI antenna located inside the PET/SPECT field-of-view to be operated without compromising any aspects of system performance or image quality compared to the stand-alone instrumentation. Here, we report a novel gamma-radiation-transparent antenna concept. The end-fed J-shape antenna is particularly adept for hybrid ultra-high field MR-PET/-SPECT applications as it enables all highly attenuating materials to be placed outside the imaging field-of-view. Furthermore, this unique configuration also provides advantages in stand-alone MR applications by reducing the amount of coupling between the cables and the antenna elements, and by lowering the potential specific absorption rate burden. The use of this new design was experimentally verified according to the important features for both ultra-high field MRI and the 511 keV transmission scan. The reconstructed attenuation maps evidently showed much lower attenuation ( ∼15 %) for the proposed array when compared to the conventional dipole antenna array since there were no high-density components. In MR, it was observed that the signal-to-noise ratio from the whole volume obtained using the proposed array was comparable to that acquired by the conventional array which was also in agreement with the simulation results. The unique feature, J-shape array, would enable simultaneous MR-PET/-SPECT experiments to be conducted without unduly compromising any aspects of system performance and image quality compared to the stand-alone instrumentation.

Design and Construction of a PET-Compatible Double-Tuned 1H/31P MR Head Coil.

Simultaneous MR-PET is an increasingly popular multimodal imaging technique that is able to combine metabolic information obtained from PET with anatomical/functional information from MRI. One of the key technological challenges of the technique is the integration of a PET-transparent MR coil system, a solution to which is demonstrated here for a double-tuned 1H/31P head coil at 3 T. Two single-resonant birdcage coils tuned to the 1H and 31P resonances were arranged in an interleaved fashion and electrically decoupled with the use of trap circuits. All high 511 keV quanta absorbing components were arranged outside the PET field-of-view in order to minimize count rate reduction. The materials inside the PET field-of-view were carefully evaluated and chosen for minimum impact on the PET image quality. As far as possible, the coil case was geometrically optimized to avoid sharp transitions in attenuation, which may potentially result in streaking artefacts during PET image reconstruction. The coil caused a count rate loss of just above 5% when inserted into the PET detector ring. Except for the anterior region, which was designed to maintain free openings for increased patient comfort, an almost uniform distribution of 511 keV attenuation was maintained around the circumference of the coil. MR-related performance for both nuclei was similar or slightly better than that of a commercial double-tuned coil, despite the MR-PET coil having a close-fitting RF screen to shield the PET and MR electronics from possible electromagnetic interferences.

Analysis of Fitting Degree of MRI and PET Images in Simultaneous MRPET Images by Machine Learning Neural Networks

Simultaneous MR-PET imaging is a fusion of MRI using various parameters and PET images using various nuclides. In this paper, we performed analysis on the fitting degree between MRI and simultaneous MR-PET images and between PET and simultaneous MR-PET images. For the fitness analysis by neural network learning, feature parameters of experimental images were extracted by discrete wavelet transform (DWT), and the extracted parameters were used as input data to the neural network. In comparing the feature values extracted by DWT for each image, the horizontal and vertical low frequencies showed similar patterns, but the patterns were different in the horizontal and vertical high-frequency and diagonal high-frequency regions. In particular, the signal value was large in the T1 and T2 weighted images of MRI. Neural network learning results for fitting degree analysis were as follows 1. T1-weighted MRI and simultaneous MR-PET image fitting degree: Regression (R) values were found to be Training 0.984, Validation 0.844, and Testing 0.886. 2. Dementia-PET image and Simultaneous MR-PET Image fitting degree: R values were found to be Training 0.970, Validation 0.803, and Testing 0.828. 3. T2-weighted MRI and concurrent MR-PET image fitting degree: R values were found to be Training 0.999, Validation 0.908, and Testing 0.766. 4. Brain tumor-PET image and Simultaneous MR-PET image fitting degree: R values were found to be Training 0.999, Validation 0.983, and Testing 0.876. An R-value closer to 1 indicates more similarity. Therefore, each image fused in the simultaneous MR-PET images verified in this study was found to be similar. Ongoing study of images acquired with pulse sequences other than the weighted images in the MRI is needed. These studies may establish a useful protocol for the acquisition of simultaneous MR-PET images.

Simultaneous task-based BOLD-fMRI and [18-F] FDG functional PET for measurement of neuronal metabolism in the human visual cortex

Studies of task-evoked brain activity are the cornerstone of cognitive neuroscience, and unravel the spatial and temporal brain dynamics of cognition in health and disease. Blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) is one of the most common methods of studying brain function in humans. BOLD-fMRI indirectly infers neuronal activity from regional changes in blood oxygenation and is not a quantitative metric of brain function. Regional variation in glucose metabolism, measured using [18-F] fluorodeoxyglucose positron emission tomography (FDG-PET), provides a more direct and interpretable measure of neuronal activity. However, while the temporal resolution of BOLD-fMRI is in the order of seconds, standard FDG-PET protocols provide a static snapshot of glucose metabolism. Here, we develop a novel experimental design for measurement of task-evoked changes in regional blood oxygenation and glucose metabolism with high temporal resolution. Over a 90-min simultaneous BOLD-fMRI/FDG-PET scan, [18F] FDG was constantly infused to 10 healthy volunteers, who viewed a flickering checkerboard presented in a hierarchical block design. Dynamic task-related changes in blood oxygenation and glucose metabolism were examined with temporal resolution of 2.5sec and 1-min, respectively. Task-related, temporally coherent brain networks of haemodynamic and metabolic connectivity were jointly coupled in the visual cortex, as expected. Results demonstrate that the hierarchical block design, together with the infusion FDG-PET technique, enabled both modalities to track task-related neural responses with high temporal resolution. The simultaneous MR-PET approach has the potential to provide unique insights into the dynamic haemodynamic and metabolic interactions that underlie cognition in health and disease.

From simultaneous to synergistic MR-PET brain imaging: A review of hybrid MR-PET imaging methodologies.

Simultaneous Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) scanning is a recent major development in biomedical imaging. The full integration of the PET detector ring and electronics within the MR system has been a technologically challenging design to develop but provides capacity for simultaneous imaging and the potential for new diagnostic and research capability. This article reviews state-of-the-art MR-PET hardware and software, and discusses future developments focusing on neuroimaging methodologies for MR-PET scanning. We particularly focus on the methodologies that lead to an improved synergy between MRI and PET, including optimal data acquisition, PET attenuation and motion correction, and joint image reconstruction and processing methods based on the underlying complementary and mutual information. We further review the current and potential future applications of simultaneous MR-PET in both systems neuroscience and clinical neuroimaging research. We demonstrate a simultaneous data acquisition protocol to highlight new applications of MR-PET neuroimaging research studies.

PET attenuation correction for rigid MR Tx/Rx coils from 176Lu background activity

One challenge for PET-MR hybrid imaging is the correction for attenuation of the 511 keV annihilation radiation by the required RF transmit and/or RF receive coils. Although there are strategies for building PET transparent Tx/Rx coils, such optimised coils still cause significant attenuation of the annihilation radiation leading to artefacts and biases in the reconstructed activity concentrations. We present a straightforward method to measure the attenuation of Tx/Rx coils in simultaneous MR-PET imaging based on the natural 176Lu background contained in the scintillator of the PET detector without the requirement of an external CT scanner or PET scanner with transmission source. The method was evaluated on a prototype 3T MR-BrainPET produced by Siemens Healthcare GmbH, both with phantom studies and with true emission images from patient/volunteer examinations. Furthermore, the count rate stability of the PET scanner and the x-ray properties of the Tx/Rx head coil were investigated. Even without energy extrapolation from the two dominant γ energies of 176Lu to 511 keV, the presented method for attenuation correction, based on the measurement of 176Lu background attenuation, shows slightly better performance than the coil attenuation correction currently used. The coil attenuation correction currently used is based on an external transmission scan with rotating 68Ge sources acquired on a Siemens ECAT HR + PET scanner. However, the main advantage of the presented approach is its straightforwardness and ready availability without the need for additional accessories.

Simultaneous acquisition of dynamic PET-MRI: arterial input function using DSC-MRI and [18F]-FET.

This work focuses on the study of simultaneous dynamic MR-PET acquisition in brain tumour patients. MR-based perfusion-weighted imaging (PWI) and PET [18F]-FET are dynamic methods, which allow to evaluate tumour metabolism in a quantitative way. In both methods, arterial input function (AIF) is necessary for quantification. However, the AIF estimation is a challenging task. In this work, we explore the possibilities to combine dynamic MR and PET AIF.

Pseudo-CT generation in brain MR-PET attenuation correction: comparison of several multi-atlas methods.

Simultaneous MR-PET imaging opens new perspectives for understanding many aspects of brain function. However, accurate brain attenuation correction (AC) is required for absolute PET quantification. Radiodensity maps for AC are not readily available in PET-MR. Various strategies have been proposed to generate substitute attenuation maps. Recently, it has been shown that multiatlas techniques for AC outperform methods based on MR imaging sequences, such as Ultrashort-Echo-Time. We recently investigated several multiatlas methods to build a patient-specific pseudoCT, all based on multiatlas registration and label propagation, and introduced a novel maximum probability method (MaxProb). Here, a new database of 40 MR/CT image pairs (atlases) was used. Pairwise nonrigid registration of each atlas MR image to the target MR image yielded a geometric transformation that we used for propagating the atlas CT into the target’s space. The synthetic CT was generated by voxelwise atlas selection and intensity averaging. We implemented a state-of-the-art algorithm along with two variants and MaxProb. A pseudoCT was generated for each subject of the database and assessed by comparison with the real CT in a leave-one-out scheme. Jaccard overlap indices were computed per tissue class (air, soft tissue, and bone). Voxel classification error was also assessed. The Jaccard indices and voxel classification error showed that MaxProb (8.31±1.12%) performed slightly better than Ref (8.65±0.93%). The influence of the number of atlases fused in pseudoCT generation was studied, showing that an optimal number improves accuracy. By adjusting the number of fused atlases, it was possible to significantly improve on Ref (8.46±0.96%). The methods now need evaluation on quantitative PET data to identify potential benefits in PET analysis.

S.23.01 Current status of simultaneous MR-PET: an opportunity for neuropharmacological studies

S.23.01 Current status of simultaneous MR-PET: an opportunity for neuropharmacological studies

Effect of MRI Acoustic Noise on Cerebral Fludeoxyglucose Uptake in Simultaneous MR-PET Imaging

Integrated scanners capable of simultaneous positron emission tomography (PET) and magnetic resonance imaging (MRI) data acquisition are now available for human use. Although the scanners' manufacturers have made substantial efforts to understand and minimize the mutual electromagnetic interference between the 2 modalities, the potential physiological inference has not been evaluated. In this study, we have studied the influence of the acoustic noise produced by the magnetic resonance (MR) gradients on brain fludeoxyglucose (FDG) uptake in the Siemens MR-BrainPET prototype. Although particular attention was paid to the primary auditory cortex (PAC), a brain-wide analysis was also performed. The effects of the MR on the PET count rate and image quantification were first investigated in phantoms. Next, 10 healthy volunteers underwent 2 simultaneous FDG-PET/MR scans in the supine position with the FDG injection occurring inside the MR-BrainPET, alternating between a "quiet" (control) environment in which no MR sequences were run during the FDG uptake phase (the first 40 minutes after radiotracer administration) and a "noisy" (test) environment in which MR sequences were run for the entire time. Cortical and subcortical regions of interest were derived from the high-resolution morphological MR data using FreeSurfer. The changes in the FDG uptake in the FreeSurfer-derived regions of interest between the 2 conditions were analyzed from parametric and static PET images, and on a voxel-by-voxel basis using SPM8 and FreeSurfer. Only minimal to no electromagnetic interference was observed for most of the MR sequences tested, with a maximum drop in count rate of 1.5% and a maximum change in the measured activity of 1.1% in the corresponding images. The region of interest-based analysis showed statistically significant increases in the right PAC in both the parametric (9.13% [4.73%]) and static (4.18% [2.87%]) images. The SPM8 analysis showed no statistically significant clusters in any images when a P < 0.05 (corrected) was used; however, a P < 0.001 (uncorrected) resolved bilateral statistically significant clusters of increased FDG uptake in the area of the PAC for the parametric image (left, 8.37% [1.55%]; right, 8.20% [1.17%]) but only unilateral increase in the static image (left, 8.68% [3.89%]). Although the operation of the BrainPET prototype is virtually unaffected by the MR scanner, the acoustic noise produced by the MR gradients causes a focal increase in the FDG uptake in the PAC, which could affect the interpretation of pathological (or brain-activation-related) changes in the FDG uptake in this region if the expected effects are of comparable amplitude.

MR-Based PET Motion Correction Procedure for Simultaneous MR-PET Neuroimaging of Human Brain

Positron Emission Tomography (PET) images are prone to motion artefacts due to the long acquisition time of PET measurements. Recently, simultaneous magnetic resonance imaging (MRI) and PET have become available in the first generation of Hybrid MR-PET scanners. In this work, the elimination of artefacts due to head motion in PET neuroimages is achieved by a new approach utilising MR-based motion tracking in combination with PET list mode data motion correction for simultaneous MR-PET acquisitions. The method comprises accurate MR-based motion measurements, an intra-frame motion minimising and reconstruction time reducing temporal framing algorithm, and a list mode based PET reconstruction which utilises the Ordinary Poisson Algorithm and avoids axial and transaxial compression. Compared to images uncorrected for motion, an increased image quality is shown in phantom as well as in vivo images. In vivo motion corrected images show an evident increase of contrast at the basal ganglia and a good visibility of uptake in tiny structures such as superior colliculi.

Bimodal MR–PET Agent for Quantitative pH Imaging

Bimodal MR–PET Agent for Quantitative pH Imaging