Unified PET-MR data processing

Partial volume effects lead in PET to an under-or overestimation of tissue activity concentration that depends on the activity distribution and the size and shape of the structures of interest, virtually affecting all neurological studies performed today. Although a myriad of partial volume effect correction methods has previously been proposed, no one method has been accepted or is routinely used for research applications and even less so in the clinical practice. We investigated the factors that affect the accuracy of these corrections:

  • segmentation of structures of interest from the anatomical MR data;
  • spatial co-registration of the MR and PET volumes;
  • characterization of the scanner’s point spread function and the assumptions made during the correction (Bowen 2013).
 
 
Anatomically-aided PET reconstruction

As a more elegant way to address this issue, in collaboration with Jinyi Qi’s group from the University of California at Davis, we have incorporated anatomical priors derived from high-resolution MRI into the PET image reconstruction model (Hutchcroft 2016)

 

MR-assisted PET Data Optimization in Simultaneous PET/MR

In addition to developing these individual methods, a major focus in our group has been on developing a unified data processing pipeline for integrating all these tools with the goal of improving the PET data quantification. We proposed an efficient algorithm to derive all the information required for performing:

  • head attenuation and motion corrections,
  • anatomy-aided reconstruction, and 
  • region-based analysis

from the standard data acquired in ~6 minutes, using one morphological MR sequence with embedded motion navigators (Chen 2019).

Using this approach, reduced variability and increased signal-to-noise ratio were seen after motion correction and anatomy-aided reconstruction. These results suggested PET data optimization may enable a more careful assessment of subtle changes in brain metabolism and allow for reduced sample sizes in future clinical trials.

Software

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Kinetic-guided image reconstruction

In the brain, kinetic modeling is frequently employed to study neuroreceptor properties and behavior. The binding potential is one such property, reflecting the density of available receptors and their affinity for the PET ligand. It can be measured by fitting a kinetic model to the PET time-activity curve with the additional input of activity concentration in arterial blood. When arterial blood is not collected as part of the study design, the kinetic model may instead be fit using an image-derived reference region that is devoid of specific binding.

However, the kinetic model selected can introduce bias into the measurements of interest. In the context of a behavioral-task study of dopamine release in healthy volunteers, we have shown that the use of MRTM2 (one of the most common reference tissue models) introduces bias into estimates change in binding potential. (Levine 2019 – abstract

Relevant publications

PET kinetic modeling

In the brain, kinetic modeling is frequently employed to study neuroreceptor properties and behavior. The binding potential is one such property, reflecting the density of available receptors and their affinity for the PET ligand. It can be measured by fitting a kinetic model to the PET time-activity curve with the additional input of activity concentration in arterial blood. When arterial blood is not collected as part of the study design, the kinetic model may instead be fit using an image-derived reference region that is devoid of specific binding.

However, the kinetic model selected can introduce bias into the measurements of interest. In the context of a behavioral-task study of dopamine release in healthy volunteers, we have shown that the use of MRTM2 (one of the most common reference tissue models) introduces bias into estimates change in binding potential. (Levine 2019 – abstract

Relevant publications

Clinical performance of motion correction for upper abdominal PET/DCE-MRI

PET and MRI are two powerful imaging technologies that are characterized by high sensitivity and the ability to provide superior anatomic detail, respectively, which might make them ideal for evaluating the upper abdomen. However, PET requires long acquisition times, including the acquisition of data from moving organs, which may result in image blurring. On the other hand, MRI, especially standard DCE-MRI, can scan the chosen field of view in a shorter time, but requires the patient’s cooperation with the respiratory instructions and the ability to suspend respiration for the acquisition time of breath-hold sequences, usually in the range 14–20 s. Moreover, even in patients with an adequate respiratory breath-hold ability, the quality and the diagnostic information of DCE-MRI are also dependent on the hemodynamics of the patient and the timing of contrast agent injection and data acquisition. These variables explain the occurrence of respiratory artifacts and erroneous phases of contrast enhancement imaging in DCE-MRI.

After developing a novel self-navigated method that simultaneously corrects both PET data and DCE-MRI data for respiratory motion without increasing acquisition times, we focused on investigating its clinical performance and to compare the motion-corrected (MoCo) and uncorrected (non-MoCo) PET, MRI and fused PET/MRI data (Catalano 2018).

In this study, the quality of MoCo PET images was found to be higher than that of non-MoCo PET images. The improved quantitation allowed by MoCo PET might be clinically relevant. In fact, besides the contribution of PET quantitation to discriminating benign from malignant lesions, assessment of treatment response relies on measured differences in SUVmax and MTV along with possible complete visual disappearance of metabolically active lesions.

Furthermore, MoCo DCE-MRI might improve the overall quality of the data in patients unable to follow breathing instructions (deaf patients, patients with a different first language, or patients unable to hear the voice of the technologist while gradients are on), and in those with hemodynamic compromise in whom timing of arterial and portal venous phase imaging is challenging. The higher quality provided by fused PET/MRI data after MoCo has important clinical implications, as in the case of small but metabolically active lesions whose anatomic correlate might be difficult to identify. This is especially true when metabolic PET data are improperly fused over the MR anatomic overlay.

Relevant publications

Motion correction for abdominal imaging

Respiratory motion correction for abdominal PET-MRI studies

PET and MRI are two powerful imaging technologies that are characterized by high sensitivity and the ability to provide superior anatomic detail, respectively, which might make them ideal for evaluating the upper abdomen. However, PET requires long acquisition times, including the acquisition of data from moving organs, which may result in image blurring. On the other hand, MRI, especially standard DCE-MRI, can scan the chosen field of view in a shorter time, but requires the patient’s cooperation with the respiratory instructions and the ability to suspend respiration for the acquisition time of breath-hold sequences, usually in the range 14–20 s. Moreover, even in patients with an adequate respiratory breath-hold ability, the quality and the diagnostic information of DCE-MRI are also dependent on the hemodynamics of the patient and the timing of contrast agent injection and data acquisition. These variables explain the occurrence of respiratory artifacts and erroneous phases of contrast enhancement imaging in DCE-MRI.

We presented and evaluated in vivo a comprehensive approach for self-gated MR motion modeling applied to concurrent respiratory motion compensation of PET and DCE-MRI data acquired simultaneously in an integrated PET/MR system.

Fully registered, motion-corrected PET images and diagnostic DCE-MR images were obtained with negligible acquisition time prolongation compared with standard breath-hold techniques. Both the MR and the PET image quality and tracer uptake quantification were improved when compared with conventional methods (Fuin 2018).

Comparison of PET images reconstructed before and after motion correction using motion vector fields obtained from 1- or 6-minutes of MR data

This approach was subsequently evaluated clinically in collaboration with Dr. Onofrio Catalano to demonstrate that motion-corrected PET/MRI produced better PET images and reduced the spatial mismatch between the two modalities (Catalano 2018).

Motion correction for cardiac PET-MRI studies

Motion correction for cardiac PET-MRI studies

We proposed an unsupervised deep learning-based approach for deformable three-dimensional cardiac MR image registration. This method learns a motion model that balances image similarity and motion estimation accuracy. We validated our approach comprehensively on three datasets and demonstrated higher motion estimation and registration accuracy relative to several popular state-of-the-art image registration methods (Morales 2019)

When used for PET motion correction, CarMEN led to an increase in the contrast-to-noise ratio in the simulated perfusion lesions (Morales et al, ISMRM/SNMMI co-provided PET/MRI Workshop, New York 2019). 

PET-based motion correction

When MR-derived motion estimates are unavailable, either in the gaps between sequences or when a given MR sequence is not amenable to motion estimation, motion can also be derived directly from the PET images themselves. Motion estimates from both the MR and the PET can be unified to provide continuous estimates of head motion throughout the duration of the scan, leveraging the higher resolution and more accurate MR-based estimates when they are available. (Levine 2017 Abstract)

Relevant publications

Motion correction for brain PET-MRI studies

MR-based motion correction for brain studies

Head motion is difficult to avoid in long PET studies, degrading the image quality and offsetting the benefit of using a high-resolution scanner. As a potential solution in an integrated MR-PET scanner, the simultaneously acquired high-temporal resolution MR data can be used for motion tracking. We proposed a data processing and rigid-body motion correction algorithm for the MR-compatible BrainPET prototype scanner and performed proof-of-principle phantom and human studies (Catana 2011).

FDG-BrainPET images before (left) and after (right) MR-assisted motion correction

This method was subsequently used in research studies aimed at assessing the role of dopamine D1 signaling in working memory (Roffman 2016) and the role of central dopamine in human bonding (Atzil 2017).  More recently, we showed the variability in the PET estimation of the cerebral metabolic rate of glucose utilization is reduced after MR-assisted motion correction in Alzheimer’s disease patients (Chen 2018).

Transmission imaging for attenuation correction

Transmission imaging for validation of MR-based attenuation correction methods​

While transmission-based techniques are still considered the true gold standard for PET attenuation correction, traditional rotating transmission sources have not been integrated into the PET/MRI scanners due to obvious engineering challenges and the desire to reduce the radiation exposure. As such techniques would be valuable for improving and validating MR-based approaches, several stationary transmission sources have been suggested as alternatives.

In the case of scanners without time-of-flight capabilities (e.g. Biograph mMR), we showed that a single torus source filled with [18F]FDG allows the acquisition of highly accurate transmission images before radiotracer administration (Bowen et al 2016)

Attenuation correction in presence of metal implants

Attenuation correction in the presence of metallic implants

The numerous foreign objects (e.g. dental implants, surgical clips and wires, orthopedic screws and plates, prosthetic devices, etc.) that can be present in the subject lead to susceptibility artifacts in the MR images that propagate as signal voids in the corresponding attenuation maps. 

We developed a method to estimate the location, shape, and linear attenuation coefficient of the implant using a joint reconstruction of the activity and attenuation algorithm. The implant PET-based attenuation map completion (IPAC) method performs a join reconstruction of radioactivity and attenuation from the emission data (Fuin et al 2017). 

MR-, CT- and IPAC-based attenuation map estimation