The combination of functional and morphological imaging technologies such as positron emission tomography (PET) and X-ray computed tomography (CT) has shown its value in the clinical and preclinical field. However, CT provides only very limited soft-tissue contrast and exposes the examined patient or laboratory animal to a high X-ray radiation dose. In comparison to CT, magnetic resonance tomography (MRI) provides excellent soft-tissue contrast and allows for nuclear magnetic resonance spectroscopy (NMRS) or functional MRI (fMRI). Thus, the combination of PET and MRI has been pursued for several years. First approaches have succeeded using conventional photo multiplier tube (PMT) technology together with light fibers to transfer scintillation light away from the high magnetic field. Latest PET/MRI developments use solid-state light detectors that can be operated even at high magnetic fields. Initial pilot studies with prototype animal PET/MRI systems have shown promising results by combining high resolution morphology with multifunctional information isochronously.

PET/MRI hybrid imaging: devices and initial results

Small-animal PET refers to imaging of animals such as rats and mice using dedicated PET scanners. Small-animal PET has been used extensively in modern biomedical research. It provides a quantitative measure of the 3-dimensional distribution of a radiopharmaceutical administered to a live subject noninvasively. In this article, we will discuss the operational and technical aspects of small-animal PET; make some comparisons between small-animal PET and human PET systems; identify the challenges of, opportunities for, and ultimate limitations in applying small-animal PET; and discuss some representative small-animal PET applications. Education objectives: After reading this article, the technologist will be able to explain the requirements and benefits of small-animal PET in biomedical research, describe the design and general characteristics of a small-animal PET system, list and describe some of the challenges of imaging small animals, and discuss several small-animal PET applications.

https://tech.snmjournals.org/content/jnmt/40/3/157.full.pdf

Small-Animal PET: What Is It, and Why Do We Need It?

Positron emission tomography (PET) is used in the clinic and in vivo small animal research to study molecular processes associated with diseases such as cancer, heart disease, and neurological disorders, and to guide the discovery and development of new treatments. This paper reviews current challenges of advancing PET technology and some of newly developed PET detectors and systems. The paper focuses on four aspects of PET instrumentation: high photon detection sensitivity; improved spatial resolution; depth-of-interaction (DOI) resolution and time-of-flight (TOF). Improved system geometry, novel non-scintillator based detectors, and tapered scintillation crystal arrays are able to enhance the photon detection sensitivity of a PET system. Several challenges for achieving high resolution with standard scintillator-based PET detectors are discussed. Novel detectors with 3-D positioning capability have great potential to be deployed in PET for achieving spatial resolution better than 1 mm, such as cadmium-zinc-telluride (CZT) and position-sensitive avalanche photodiodes (PSAPDs). DOI capability enables a PET system to mitigate parallax error and achieve uniform spatial resolution across the field-of-view (FOV). Six common DOI designs, as well as advantages and limitations of each design, are discussed. The availability of fast scintillation crystals such as LaBr(3), and the silicon photomultiplier (SiPM) greatly advances TOF-PET development. Recent instrumentation and initial results of clinical trials are briefly presented. If successful, these technology advances, together with new probe molecules, will substantially enhance the molecular sensitivity of PET and thus increase its role in preclinical and clinical research as well as evaluating and managing disease in the clinic.

/pdf/recent-developments-in-pet-instrumentation-20wnnxwyiz.pdf

Recent Developments in PET Instrumentation

Positron emission tomography (PET) is used in the clinic and in vivo small animal research to study certain molecular processes associated with diseases such as cancer, heart disease, and neurological disorders and guide the discovery and development of new treatments. New PET molecular probes and associated small animal imaging assays are under development to target, visualize, and quantify subtle molecular and cellular processes such as protein-protein interactions in signal transduction pathways, cancer cell trafficking, therapeutic stem cells and their progeny, interaction of the immune system and tumor cells, and gene delivery and expression in living animals. These next-generation PET molecular imaging assays require an order of magnitude increase in PET's ability to detect, visualize, and quantify low concentrations of probe interacting with its target, which we will refer to as molecular sensitivity , in order to study the subtle signatures associated with these molecular processes. The molecular sensitivity is determined by a combination of the probe and biological/physiological properties of the subject that determine its specificity for the target, and the performance capabilities of the imaging system that determine how well the resulting signal can be measured. This paper focuses on the second aspect: the challenges of advancing PET technology and some of the new imaging system technologies under investigation to substantially enhance PET's molecular sensitivity. If successful, these novel imaging system technology advances, together with new probe molecules that target specific molecular processes associated with disease, will substantially enhance the molecular sensitivity of PET and thus increase its role in preclinical and clinical research as well as evaluating and managing disease in the clinic.

New Imaging Technologies to Enhance the Molecular Sensitivity of Positron Emission Tomography

Realizing the full potential of high-resolution positron emission tomography (PET) systems involves accurately positioning events in which the annihilation photon deposits all its energy across multiple detector elements. Reconstructing the complete sequence of interactions of each photon provides a reliable way to select the earliest interaction because it ensures that all the interactions are consistent with one another. Bayesian estimation forms a natural framework to maximize the consistency of the sequence with the measurements while taking into account the physics of γ -ray transport. An inherently statistical method, it accounts for the uncertainty in the measured energy and position of each interaction. An algorithm based on maximum a posteriori (MAP) was evaluated for computer simulations. For a high-resolution PET system based on cadmium zinc telluride detectors, 93.8% of the recorded coincidences involved at least one photon multiple-interactions event (PMIE). The MAP estimate of the first interaction was accurate for 85.2% of the single photons. This represents a two-fold reduction in the number of mispositioned events compared to minimum pair distance, a simpler yet efficient positioning method. The point-spread function of the system presented lower tails and higher peak value when MAP was used. This translated into improved image quality, which we quantified by studying contrast and spatial resolution gains. (Some figures in this article are in colour only in the electronic version)

/pdf/bayesian-reconstruction-of-photon-interaction-sequences-for-43ytlietdp.pdf

Bayesian reconstruction of photon interaction sequences for high-resolution PET detectors.

We are studying two new detector technologies that directly measure the three-dimensional coordinates of 511 keV photon interactions for high-resolution positron emission tomography (PET) systems designed for small animal and breast imaging. These detectors are based on (1) lutetium oxyorthosilicate (LSO) scintillation crystal arrays coupled to position-sensitive avalanche photodiodes (PSAPD) and (2) cadmium zinc telluride (CZT). The detectors have excellent measured 511 keV photon energy resolutions ( 8% photon sensitivity for the LSO-PSAPD box configuration and >15% for CZT box geometry, using a 350-650 keV energy window setting. These simulation results compare well with analytical estimations. The trend is different for a clinical whole-body PET system that uses conventional LSO-PMT block detectors with larger crystal elements. Simulations predict roughly the same sensitivity for both box and cylindrical detector configurations. This results from the fact that a large system diameter (>80 cm) results in relatively small inter-module gaps in clinical whole-body PET. In addition, the relatively large block detectors (typically >5 x 5 cm(2) cross-sectional area) and large crystals (>4 x 4 x 20 mm(3)) enable a higher fraction of detector scatter photons to be absorbed compared to a small animal system. However, if the four detector sides (panels) of a box-shaped system geometry are configured to move with respect to each other, to better fit the transaxial FOV to the actual size of the object to be imaged, a significant increase in photon sensitivity is possible. Simulation results predict a 60-100% relative increase of photon sensitivity for the proposed small animal PET box configurations and >60% increase for a clinical whole-body system geometry. Thus, simulation results indicate that for a PET system built from rectangular-shaped detector modules, arranging them into a box-shaped system geometry may help us to significantly boost photon sensitivity for both small animal and clinical PET systems.

/pdf/effects-of-system-geometry-and-other-physical-factors-on-233s7z98ao.pdf

Effects of system geometry and other physical factors on photon sensitivity of high-resolution positron emission tomography.

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Effects of system geometry and other physical factors on photon sensitivity of high-resolution positron emission tomography.