The purpose of this article is to provide a brief overview of the background, basic principles, technological evolution, clinical capabilities, and future directions for functional tumor imaging as PET evolves from the conventional photomultiplier tube-based platform into a fully digital detector acquisition platform. The recent introduction of solid-state digital photon counting PET detector is the latest evolution of clinical PET which enables faster time-of-flight timing resolution that leads to more precise localization of the annihilation events and further contributes to reduction in partial volume and thus makes high definition and ultrahigh definition PET imaging feasible with current standard acquisition procedures. The technological advances of digital PET can be further leveraged by optimizing many of the acquisition and reconstruction methodologies to achieve faster image acquisition to improve cancer patient throughput, lower patient dose in accordance with ALARA, and improved quantitative accuracy to enable biomarker capability. Digital PET technology will advance molecular imaging capabilities beyond oncology and enable Precision Nuclear Medicine.
The purpose of this article is to briefly introduce the current technological evolution that is enabled by digital detector technology and discuss its applicability to clinical positron emission tomography/computed tomography (PET/CT). Although PET/CT utilization has been primarily oncologic, functional molecular imaging has the opportunity for expanded utilization in both oncologic and nononcologic applications and will demand reduced ionizing radiotracer doses and improved quantification. The paradigm of Precision Nuclear Medicine incorporates new strategies to advance functional molecular imaging with more detailed visualization and more robust quantification of disease burden. These aspects are essential both for diagnostic and for therapy management opportunities including the further evolution as validated biomarkers. Even today, there are considerable unmet clinical needs such as the frequently observed indeterminate PET lesion, detectability of subcentimeter lesions, and lack of biomarker validation for response assessment. While many technologies have been rapidly moving away from cathode-ray tubes and analog signal processing, nuclear medicine and PET are still predominantly using the analog photomultiplier tube acquisition technologies. The recent introduction of solid-state detectors is a transformative technology change for clinical nuclear medicine. As with many other technology changes, solid-state and digital acquisition technologies can be implemented in different ways. One major driving force to pursue the replacement of the photomultiplier tube technology was the goal of integrated PET/magnetic resonance imaging (MRI) and next-generation PET/CT systems. While the acquisition chain consists of multiple components, especially the crystal characteristics, this article highlights the clinical opportunities enabled by this change of the detector technology. The most recent technology advance for PET/CT has been the clinical demonstration of a solid-state system which also has the best clinical system time-of-flight timing capabilities. This article summarizes our initial experiences with a focus on demonstrating the overall opportunities supported by next-generation digital PET technology.
Photomultiplier tube (PMT) detectors have been used since the early days of PET [
The photomultiplier tube detector unit from a cPET system (a) which has recently been replaced with a solid-state DPC PET detector unit (b) in the next-generation dPET/CT system. (c) A closer view of the DPC PET detector (Philips Healthcare, Cleveland, Ohio, USA). The DPC PET detector unit enables fully digital 1 : 1 coupling with the scintillation crystals within the dPET detector ring assembly.
Whole-body PET became clinically feasible in the late 1980s and subsequently evolved from a 2D to a 3D multiring platform [
With the growth of MRI and the superb soft tissue contrast achievable, the vision of hybrid PET/MR systems rapidly evolved in the last decade [
The initial lack of full digitization in the SiPM detectors led to the next technological leap with the introduction of digital photon counting (DPC) detector technology [
Here, we briefly present 7 features of clinical PET systems that are particularly relevant for understanding the clinical implications of new PET detector technologies [
Spatial resolution of a PET scanner is an intrinsic feature of the detector chain which reflects the ability of the system to physically differentiate between two sources within the minimum distance between two points in a reconstructed image [
Sensitivity of a PET system represents the ability to detect the true annihilation event rate. It is normally expressed in counts per unit time per unit of activity present in a source and depends on factors like solid angle, system photon detection efficiency, and dead time. Sensitivity in PET was substantially improved with the introduction of 3D acquisition; however, the sensitivity profile usually degrades from a peak in the center to both edges. In particular, 3D PET acquisitions have a rapid decrease in linear sensitivity due to poor counting statistics at the edges, thus requiring an overlap in longitudinal field of view between adjacent bed positions. Similarly, sensitivity decreases linearly within the axial field of view. An early observation and key advantage of the dPET detector technology is its virtually zero dead time, improving dPET system sensitivity [
Image noise of a PET system is usually characterized by the NECR which is substantially improved with dPET systems [
One goal to advance clinical nuclear medicine is to image faster and thus reduce patient motion, patient discomfort, table time, and the need for sedation/anesthesia [
Despite many technological advances in PET, today’s clinical PET imaging reconstruction approaches utilize matrix sizes smaller than or equal to 200 and voxel lengths of 3-4 mm [
The clinical benefit of ToF has been well recognized in the recent years [
Another approach for better utilizing the higher sensitivity and precision of the dPET detector technology is to substantially reduce radiotracer dosing [
In summary, it has to be highlighted that the dPET technology enables the refinement of many different components that impact overall image quality, lesion detectability, and quantification.
Our team has extensive experience performing more than 150 intraindividual comparison studies between dPET/CT and cPET/CT systems currently focusing on using standard of care, standard dose, and standard definition imaging [
Digital PET has the ability to use larger reconstruction matrices with smaller voxel volumes which enables a more robust visualization of smaller metabolically active lesions. Currently, most cPET images are reconstructed using standard definition matrix sizes of 144–200. We anticipate that dPET imaging will routinely use high definition reconstruction with matrix sizes between 200 and 400 while using unchanged acquisition times. Initial results indicate that even ultrahigh definition imaging with matrix sizes greater than 400 can be readily accomplished for current whole-body imaging protocols leading to voxel volumes comparable to CT and/or MRI [
Intraindividual comparison in a patient scanned on the cPET/CT (Gemini 64 ToF, Philips Healthcare, Cleveland, Ohio, USA) system and a precommercial release dPET/CT (Vereos, Philips Healthcare, Cleveland, Ohio, USA) system using different reconstruction matrix/voxel volume sizes with a 3D line-of-response TOF blob-based algorithm [
Based on the improved sensitivity and precision of the dPET detector platform, there is potential for enabling faster whole-body PET image acquisitions [
A well-established limitation of cPET is the deterioration of the recovery coefficient as lesion size decreases which weakens the quantitative precision for response assessment. This challenge not only affects small lesions but also affects quantitative precision when evaluating heterogeneous lesions. Although recovery coefficient and quantification are impacted by many components including detector characteristics, count density, timing resolution of ToF, and reconstruction approach, dPET technology has the potential to advance the quantitative precision for smaller and heterogeneous lesions in order to facilitate more consistency across multisite and multisystem clinical trials (e.g., EARL harmonization). It has been demonstrated that dPET has the highest overall system performance with consistently improved recovery coefficients when compared with cPET [
The current vision for the use of digital PET technology is either to implement it within hybrid MR systems or to improve the existing diagnostic/therapy management capabilities of PET/CT systems. It is our opinion that the DPC technology is truly the next generation in the evolution of PET imaging systems both as hybrid PET/CT and as PET/MR. The technological advances can be further leveraged by optimizing many of the PET acquisition and reconstruction methodologies to achieve disease-specific and organization-specific goals (e.g., faster image acquisition to improve patient throughput, lower patient dose in accordance with “as low as reasonably achievable” (ALARA), and improved quantitative accuracy to enable biomarker capability). PET image quality has not fundamentally changed over the last two decades and is poised to leap forward with high definition and even ultrahigh definition imaging. If we enable a substantial reduction in radiotracer dose, we have an opportunity to utilize PET more broadly in nononcologic applications (Figure
Nononcologic clinical opportunities for lower dose/higher definition imaging enabled by next-generation dPET include (a) neurologic, (b) cardiovascular, and (c) orthopedic/sports medicine indications. Digital PET cases demonstrated were imaged using standard 18F-FDG doses of 448 MBq and 477 MBq for (a) and (b), respectively, and ultralow 18F-FDG dose of 100 MBq for (c). The dPET acquisitions were obtained at 55 min after injection for (a), 53 min after injection for (b), and 60 min after injection for (c). The dPET emission scans were acquired with 90 s per bed position for (a) and (b) but (c) was a limited single bed acquisition for 15 min. Low dose CT attenuation scans were acquired using 120 kV and 50 mA with dose modulation and using iterative iDose4 reconstruction.
This article highlights the fundamental technology innovations that led to the current development of next-generation digital PET systems. The wider clinical availability of dPET may be the inflection point to move clinical PET practice beyond oncology and into other nononcologic molecular imaging applications. In summary, digital PET is a transformative technology that will advance the paradigm of Precision Nuclear Medicine to address the unmet clinical needs for better tumor lesion detectability, improved lesion characterization especially for indeterminate lesions, more rapid biomarker validation for therapy response assessment, and radiotracer dose reduction in accordance with ALARA.
Fluorine-18-fluorodeoxyglucose
As low as reasonably achievable
Avalanche photodiode
Computed tomography
Conventional positron emission tomography
Digital photon counting
Digital positron emission tomography
Full width half max
Magnetic resonance
Magnetic resonance imaging
Positron emission tomography
Photomultiplier tube
Point spread function
Silicon photomultiplier.
The authors report no conflicts of interest regarding the publication of this paper.
Chadwick L. Wright is supported by (1) the American Cancer Society (Grant no. IRG-67-003-50) and (2) the National Institutes of Health (NIH)/National Cancer Institute (NCI), Clinical Loan Repayment Program. Chadwick L. Wright, Katherine Binzel, Jun Zhang, and Michael V. Knopp are also supported by the Wright Center of Innovation in Biomedical Imaging and Ohio ODSA TECH 09-028, TECH 10-012, and TECH 13-060 and the National Institutes of Health R01CA195513 and 5U24CA180803.