Sune Høgild Keller

Combined PET/MR imaging in neurology: MR-based attenuation correction implies a strong spatial bias when ignoring bone☆

AIM Combined PET/MR systems have now become available for clinical use. Given the lack of integrated standard transmission (TX) sources in these systems, attenuation and scatter correction (AC) must be performed using the available MR-images. Since bone tissue cannot easily be accounted for during MR-AC, PET quantification can be biased, in particular, in the vicinity of the skull. Here, we assess PET quantification in PET/MR imaging of patients using phantoms and patient data. MATERIALS AND METHODS Nineteen patients referred to our clinic for a PET/CT exam as part of the diagnostic evaluation of suspected dementia were included in our study. The patients were injected with 200MBq [(18)F]FDG and imaged with PET/CT and PET/MR in random sequence within 1h. Both, PET/CT and PET/MR were performed as single-bed acquisitions without contrast administration. PET/CT and PET/MR data were reconstructed following CT-based and MR-based AC, respectively. MR-AC was performed based on: (A) standard Dixon-Water-Fat segmentation (DWFS), (B) DWFS with co-registered and segmented CT bone values superimposed, and (C) with co-registered full CT-based attenuation image. All PET images were reconstructed using AW-OSEM, with neither resolution recovery nor time-of-flight option employed. PET/CT (D) or PET/MR (A-C) images were decay-corrected to the start time of the first examination. PET images following AC were evaluated visually and quantitatively using 10 homeomorphic regions of interest drawn on a transaxial T1w-MR image traversing the central basal ganglia. We report the relative difference (%) of the mean ROI values for (A)-(C) in reference to PET/CT (D). In a separate phantom experiment a 2L plastic bottle was layered with approximately 12mm of Gypsum plaster to mimic skull bone. The phantom was imaged on PET/CT only and standard MR-AC was performed by replacing hyperdense CT attenuation values corresponding to bone (plaster) with attenuation values of water. PET image reconstruction was performed with CT-AC (D) and CT-AC using the modified CT images corresponding to MR-AC using DWFS (A). RESULTS PET activity values in patients following MR-AC (A) showed a substantial radial dependency when compared to PET/CT. In all patients cortical PET activity was lower than the activity in the central region of the brain (10-15%). When adding bone attenuation values to standard MR-AC (B and C) the radial gradient of PET activity values was removed. Further evaluation of PET/MR activity following MR-AC (A) relative to MR-AC (C) using the full CT for attenuation correction showed an underestimation of 25% in the cortical regions and 5-10% in the central regions of the brain. Observations in patients were replicated by observations from the phantom study. CONCLUSION Our phantom and patient data demonstrate a spatially varying bias of the PET activity in PET/MR images of the brain when bone tissue is not accounted for during attenuation correction. This has immediate implications for PET/MR imaging of the brain. Therefore, refinements to existing MR-AC methods or alternative strategies need to be found prior to adopting PET/MR imaging of the brain in clinical routine and research.

64Cu-DOTATATE PET/MRI for Detection of Activated Macrophages in Carotid Atherosclerotic Plaques Studies in Patients Undergoing Endarterectomy

Objective— A feature of vulnerable atherosclerotic plaques of the carotid artery is high activity and abundance of lesion macrophages. There is consensus that this is of importance for plaque vulnerability, which may lead to clinical events, such as stroke and transient ischemic attack. We used positron emission tomography (PET) and the novel PET ligand [64Cu] [1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid]-d-Phe1,Tyr3-octreotate (64Cu-DOTATATE) to specifically target macrophages via the somatostatin receptor subtype-2 in vivo. Approach and Results— Ten patients underwent simultaneous PET/MRI to measure 64Cu-DOTATATE uptake in carotid artery plaques before carotid endarterectomy. 64Cu-DOTATATE uptake was significantly higher in symptomatic plaque versus the contralateral carotid artery (P<0.001). Subsequently, a total of 62 plaque segments were assessed for gene expression of selected markers of plaque vulnerability using real-time quantitative polymerase chain reaction. These results were compared with in vivo 64Cu-DOTATATE uptake calculated as the mean standardized uptake value. Univariate analysis of real-time quantitative polymerase chain reaction and PET showed that cluster of differentiation 163 (CD163) and CD68 gene expression correlated significantly but weakly with mean standardized uptake value in scans performed 85 minutes post injection (P<0.001 and P=0.015, respectively). Subsequent multivariate analysis showed that CD163 correlated independently with 64Cu-DOTATATE uptake (P=0.031) whereas CD68 did not contribute significantly to the final model. Conclusions— The novel PET tracer 64Cu-DOTATATE accumulates in atherosclerotic plaques of the carotid artery. CD163 gene expression correlated independently with 64Cu-DOTATATE uptake measured by real-time quantitative polymerase chain reaction in the final multivariate model, indicating that 64Cu-DOTATATE PET is detecting alternatively activated macrophages. This association could potentially improve noninvasive identification and characterization of vulnerable plaques.

Age and sex effects on 5-HT(4) receptors in the human brain: a [(11)C]SB207145 PET study

Experimental studies indicate that the 5-HT4 receptor activation influence cognitive function, affective symptoms, and the development of Alzheimers disease (AD). The prevalence of AD increases with aging, and women have a higher predisposition to both AD and affective disorders than men. This study aimed to investigate sex and age effects on 5-HT4 receptor-binding potentials in striatum, the limbic system, and neocortex. Positron-emission tomographic scans were conducted using the radioligand [11C]SB207145 in a cohort of 30 healthy subjects (mean age 44 years; range 20 to 86 years; 14 men and 16 women). The output parameter, BPND, was modeled using the simplified reference tissue model, and partial volume correction was performed with the Muller-Gartner method. A decline with age of 1% per decade was found only in striatum. Women had a 13% lower 5-HT4 receptor binding in the limbic system. The lower limbic 5-HT4 receptor binding in women supports a role for 5-HT4 receptors in the sex-specific differences in emotional control and might contribute to the higher prevalence of affective diseases and AD in women. The relatively stable 5-HT4 receptor binding with aging contrasts others in subtypes of receptors, which generally decrease with aging.

PET/MRI in cancer patients: first experiences and vision from Copenhagen

Combined PET/MRI systems are now commercially available and are expected to change the medical imaging field by providing combined anato-metabolic image information. We believe this will be of particular relevance in imaging of cancer patients. At the Department of Clinical Physiology, Nuclear Medicine & PET at Rigshospitalet in Copenhagen we installed an integrated PET/MRI in December 2011. Here, we describe our first clinical PET/MR cases and discuss some of the areas within oncology where we envision promising future application of integrated PET/MR imaging in clinical routine. Cases described include brain tumors, pediatric oncology as well as lung, abdominal and pelvic cancer. In general the cases show that PET/MRI performs well in all these types of cancer when compared to PET/CT. However, future large-scale clinical studies are needed to establish when to use PET/MRI. We envision that PET/MRI in oncology will prove to become a valuable addition to PET/CT in diagnosing, tailoring and monitoring cancer therapy in selected patient populations.

Spatial resolution of the HRRT PET scanner using 3D-OSEM PSF reconstruction

In this paper, the resolution of the Siemens high resolution research tomograph (HRRT) was centrally (r < 60 mm) homogenous with a FWHM of 1.4 mm for 18F-FDG in air. This was where the main part of the brain is located if the patient has been positioned correctly. The 1.4 mm resolution was obtained using the newly develop 3D-OSEM PSF reconstruction algorithm, which was a significant improvement over 3D-OSEM reconstruction without PSF. The algorithm uses a simple PSF model that was the same for all the pixels in the FOV and does not regulate for the circular/octagonal scanner geometry. This supports that the FWHM of the radial axis is increasing with the distance from the center for r > 60mm.

Methods for Motion Correction Evaluation Using 18F-FDG Human Brain Scans on a High-Resolution PET Scanner

Many authors have reported the importance of motion correction (MC) for PET. Patient motion during scanning disturbs kinetic analysis and degrades resolution. In addition, using misaligned transmission for attenuation and scatter correction may produce regional quantification bias in the reconstructed emission images. The purpose of this work was the development of quality control (QC) methods for MC procedures based on external motion tracking (EMT) for human scanning using an optical motion tracking system. Methods: Two scans with minor motion and 5 with major motion (as reported by the optical motion tracking system) were selected from 18F-FDG scans acquired on a PET scanner. The motion was measured as the maximum displacement of the markers attached to the subjects head and was considered to be major if larger than 4 mm and minor if less than 2 mm. After allowing a 40- to 60-min uptake time after tracer injection, we acquired a 6-min transmission scan, followed by a 40-min emission list-mode scan. Each emission list-mode dataset was divided into 8 frames of 5 min. The reconstructed time-framed images were aligned to a selected reference frame using either EMT or the AIR (automated image registration) software. The following 3 QC methods were used to evaluate the EMT and AIR MC: a method using the ratio between 2 regions of interest with gray matter voxels (GM) and white matter voxels (WM), called GM/WM; mutual information; and cross correlation. Results: The results of the 3 QC methods were in agreement with one another and with a visual subjective inspection of the image data. Before MC, the QC method measures varied significantly in scans with major motion and displayed limited variations on scans with minor motion. The variation was significantly reduced and measures improved after MC with AIR, whereas EMT MC performed less well. Conclusion: The 3 presented QC methods produced similar results and are useful for evaluating tracer-independent external-tracking motion-correction methods for human brain scans.

Attenuation Correction for the HRRT PET-Scanner Using Transmission Scatter Correction and Total Variation Regularization

In the standard software for the Siemens high-resolution research tomograph (HRRT) positron emission tomography (PET) scanner the most commonly used segmentation in the μ-map reconstruction for human brain scans is maximum a posteriori for transmission (MAP-TR). Bias in the lower cerebellum and pons in HRRT brain images have been reported. The two main sources of the problem with MAP-TR are poor bone/soft tissue segmentation below the brain and overestimation of bone mass in the skull. Method: We developed the new transmission processing with total variation (TXTV) method that introduces scatter correction in the μ-map reconstruction and total variation filtering to the transmission processing. Results: Comparing MAP-TR and the new TXTV with gold standard CT-based attenuation correction, we found that TXTV has less bias as compared to MAP-TR. We also compared images acquired at the HRRT scanner using TXTV to the GE Advance scanner images and found high quantitative correspondence. TXTV has been used to reconstruct more than 4000 HRRT scans at seven different sites with no reports of biases. Conclusion: TXTV-based reconstruction is recommended for human brain scans on the HRRT.

Deinterlacing Using Variational Methods

We present a variational framework for deinterlacing that was originally used for inpainting and subsequently redeveloped for deinterlacing. From the framework, we derive a motion adaptive (MA) deinterlacer and a motion compensated (MC) deinterlacer and test them together with a selection of known deinterlacers. To illustrate the need for MC deinterlacing, the problem of details in motion (DIM) is introduced. It cannot be solved by MA deinterlacers or any simpler deinterlacers but only by MC deinterlacers. The major problem in MC deinterlacing is computing reliable optical flow [motion estimation (ME)] in interlaced video. We discuss a number of strategies for computing optical flows on interlaced video hoping to shed some light on this problem. We produce results on challenging real world video data with our variational MC deinterlacer that in most cases are indistinguishable from the ground truth.

Video Super-Resolution Using Simultaneous Motion and Intensity Calculations

In this paper, we propose an energy-based algorithm for motion-compensated video super-resolution (VSR) targeted on upscaling of standard definition (SD) video to high-definition (HD) video. Since the motion (flow field) of the image sequence is generally unknown, we introduce a formulation for the joint estimation of a super-resolution (SR) sequence and its flow field. Via the calculus of variations, this leads to a coupled system of partial differential equations for image sequence and motion estimation. We solve a simplified form of this system and, as a by-product, we indeed provide a motion field for super-resolved sequences. To the best of our knowledge, computing super-resolved flows has not been done before. Most advanced SR methods found in literature cannot be applied to general video with arbitrary scene content and/or arbitrary optical flows, as it is possible with our simultaneous VSR method. A series of experiments shows that our method outperforms other VSR methods when dealing with general video input and that it continues to provide good results even for large scaling factors up to 8 × 8.

Investigation of motion induced errors in scatter correction for the HRRT brain scanner

Patient motion during PET scans introduces errors in the attenuation correction and image blurring leading to false changes in regional radioactivity concentrations. However, the potential effect that motion has on simulation-based scatter correction is not fully appreciated. Specifically for tracers with high uptake close to the edge of head (e.g. scalp and nose) as observed with [11C]Verapamil, mismatches between transmission and emission data can lead to significant quantification errors and image artefacts due to over scatter correction. These errors are linked with unusually high values in the scatter scaling factors (SSF) returned during the single scatter simulation process implemented in the HRRT image reconstruction. Reconstruction of μ-map with TXTV (an alternative μ-map reconstruction using non-linear filtering rather than brain segmentation and scatter correction of the transmission data) was found to improve the scatter simulation results for [11C]Verapamil and [18F]FDG. The errors from patient motion were characterised and quantified through simulations by applying realistic transformations to the attenuation map (μ-map). This generated inconsistencies between the emission and transmission data, and introduced large over-corrections of scatter similar to some cases observed with [11C]Verapamil. Automated Image Registration (AIR) based motion correction was also implemented, and found to remove the artifact and recover quantification in dynamic studies after aligning all the PET images to a common reference space.