Since the 1990s, hybrid imaging by means of software and hardware image fusion alike allows the intrinsic combination of functional and anatomical image information. This review summarises in three parts the state of the art of dual-technique imaging with a focus on clinical applications. We will attempt to highlight selected areas of potential improvement of combined imaging technologies and new applications. In this third part, we discuss briefly the origins of combined positron emission tomography (PET)/magnetic resonance imaging (MRI). Unlike PET/computed tomography (CT), PET/MRI started out from developments in small-animal imaging technology, and, therefore, we add a section on advances in dual- and multi-modality imaging technology for small animals. Finally, we highlight a number of important aspects beyond technology that should be addressed for a sustained future of hybrid imaging. In short, we predict that, within 10 years, we may see all existing multi-modality imaging systems in clinical routine, including PET/MRI. Despite the current lack of clinical evidence, integrated PET/MRI may become particularly important and clinically useful in improved therapy planning for neurodegenerative diseases and subsequent response assessment, as well as in complementary loco-regional oncology imaging. Although desirable, other combinations of imaging systems, such as single-photon emission computed tomography (SPECT)/MRI may be anticipated, but will first need to go through the process of viable clinical prototyping. In the interim, a combination of PET and ultrasound may become available. As exciting as these new possible triple-technique-imaging systems sound, we need to be aware that they have to be technologically feasible, applicable in clinical routine and cost-effective.

Information has been collected from PET/MRI operational sites to identify its present and future applications. This may help to focus discussions on common interests of the PET/MRI community.

Methods

A web-based survey of PET/MRI users was conducted from June to October 2015. The survey was composed of 26 questions related to the PET/MRI center, present use and imaging protocols, and perspectives on key applications.

Results

Responses were collected from 39 international sites that operated PET/MRI for a median of 30 mo (range, 2-62 mo). Most installations were located in public institutions with an academic focus (n = 26, 67%). Systems were primarily operated by nuclear medicine departments (n = 13, 33%), jointly by nuclear medicine and radiology (n = 11, 28%), and radiology only (n = 10, 26%). PET/MRI operation was equally focused on clinic routine and research (47% vs. 45% of sites, respectively). Sites reported a strong focus on oncology (76% of research and 88% of clinical applications). Other applications included neurology (9% clinical, 12% research) and cardiology (3% clinical, 6% research). Perceived superiority over PET/CT was identified as the strongest driver for clinical adoption. Over half the operators expect PET/MRI to excel in clinical routine within 3-5 y. Emerging key applications for future PET/MRI use were cardiovascular disease and imaging of inflammation.

Conclusion

An international survey of early PET/MR adopters reveals a mixed use of this combined imaging modality, with a focus on oncology. The future of PET/MRI is seen in expanded application for oncology and neurology, but also cardiovascular disease and inflammation.

Since the 1990s, hybrid imaging by means of software and hardware image fusion alike allows the intrinsic combination of functional and anatomical image information. This review summarises in three parts the state-of-the-art of dual-technique imaging, with a focus on clinical applications. We will attempt to highlight selected areas of potential improvement of combined imaging technologies and new applications. In this first part, we briefly review the origins of hybrid imaging and comment on the status and future development of single photon emission tomography (SPECT)/computed tomography (CT). In short, we could predict that, within 10 years, we may see all existing dual-technique imaging systems, including SPECT/CT, in clinical routine use worldwide. SPECT/CT, in particular, may evolve into a whole-body imaging technique with supplementary use in dosimetry applications.

Since the 1990s, hybrid imaging by means of software and hardware image fusion alike allows the intrinsic combination of functional and anatomical image information. This review summarises the state-of-the-art of dual-modality imaging with a focus on clinical applications. We highlight selected areas for potential improvement of combined imaging technologies and new applications. In the second part, we briefly review the background of dual-modality PET/CT imaging, discuss its main applications and attempt to predict technological and methodological improvements of combined PET/CT imaging. After a decade of clinical evaluation, PET/CT will continue to have a significant impact on patient management, mainly in the area of oncological diseases. By adopting more innovative acquisition schemes and data processing PET/CT will become a fast and dose-efficient imaging method and an integral part of state-of-the-art clinical patient management.

We introduce multiple-organ objective segmentation (MOOSE) software that generates subject-specific, multiorgan segmentation using data-centric artificial intelligence principles to facilitate high-throughput systemic investigations of the human body via whole-body PET imaging. Methods: Image data from 2 PET/CT systems were used in training MOOSE. For noncerebral structures, 50 whole-body CT images were used, 30 of which were acquired from healthy controls (14 men and 16 women), and 20 datasets were acquired from oncology patients (14 men and 6 women). Noncerebral tissues consisted of 13 abdominal organs, 20 bone segments, subcutaneous fat, visceral fat, psoas muscle, and skeletal muscle. An expert panel manually segmented all noncerebral structures except for subcutaneous fat, visceral fat, and skeletal muscle, which were semiautomatically segmented using thresholding. A majority-voting algorithm was used to generate a reference-standard segmentation. From the 50 CT datasets, 40 were used for training and 10 for testing. For cerebral structures, 34 ¹⁸F-FDG PET/MRI brain image volumes were used from 10 healthy controls (5 men and 5 women imaged twice) and 14 nonlesional epilepsy patients (7 men and 7 women). Only ¹⁸F-FDG PET images were considered for training: 24 and 10 of 34 volumes were used for training and testing, respectively. The Dice score coefficient (DSC) was used as the primary metric, and the average symmetric surface distance as a secondary metric, to evaluate the automated segmentation performance. Results: An excellent overlap between the reference labels and MOOSE-derived organ segmentations was observed: 92% of noncerebral tissues showed DSCs of more than 0.90, whereas a few organs exhibited lower DSCs (e.g., adrenal glands [0.72], pancreas [0.85], and bladder [0.86]). The median DSCs of brain subregions derived from PET images were lower. Only 29% of the brain segments had a median DSC of more than 0.90, whereas segmentation of 60% of regions yielded a median DSC of 0.80-0.89. The results of the average symmetric surface distance analysis demonstrated that the average distance between the reference standard and the automatically segmented tissue surfaces (organs, bones, and brain regions) lies within the size of image voxels (2 mm). Conclusion: The proposed segmentation pipeline allows automatic segmentation of 120 unique tissues from whole-body ¹⁸F-FDG PET/CT images with high accuracy.

Apolipoprotein AV (APOA5) lowers plasma triglyceride (TG) levels by binding to the angiopoietin-like protein 3/8 complex (ANGPTL3/8) and suppressing its capacity to inhibit lipoprotein lipase (LPL) catalytic activity and its ability to detach LPL from binding sites within capillaries. However, the sequences in APOA5 that are required for suppressing ANGPTL3/8 activity have never been defined. A clue to the identity of those sequences was the presence of severe hypertriglyceridemia in two patients harboring an APOA5 mutation that truncates APOA5 by 35 residues (APOA5Δ35). We found that wild-type (WT) human APOA5, but not APOA5Δ35, suppressed ANGPTL3/8s ability to inhibit LPL catalytic activity. To pursue that finding, we prepared a mutant mouse APOA5 protein lacking 40 C-terminal amino acids (APOA5Δ40). Mouse WT-APOA5, but not APOA5Δ40, suppressed ANGPTL3/8s capacity to inhibit LPL catalytic activity and sharply reduced plasma TG levels in mice. WT-APOA5, but not APOA5Δ40, increased intracapillary LPL levels and reduced plasma TG levels in Apoa5-/- mice (where TG levels are high and intravascular LPL levels are low). Also, WT-APOA5, but not APOA5Δ40, blocked the ability of ANGPTL3/8 to detach LPL from cultured cells. Finally, an antibody against a synthetic peptide corresponding to the last 26 amino acids of mouse APOA5 reduced intracapillary LPL levels and increased plasma TG levels in WT mice. We conclude that C-terminal sequences in APOA5 are crucial for suppressing ANGPTL3/8 activity in vitro and for regulating intracapillary LPL levels and plasma TG levels in vivo.