Bone marrow adipose tissue (BMAT) comprises >10% of total adipose mass, yet unlike white or brown adipose tissues (WAT or BAT) its metabolic functions remain unclear. Herein, we address this critical gap in knowledge. Our transcriptomic analyses revealed that BMAT is distinct from WAT and BAT, with altered glucose metabolism and decreased insulin responsiveness. We therefore tested these functions in mice and humans using positron emission tomography-computed tomography (PET/CT) with 18 F-fluorodeoxyglucose. This revealed that BMAT resists insulin-and cold-stimulated glucose uptake, while further in vivo studies showed that, compared to WAT, BMAT resists insulin-stimulated Akt phosphorylation. Thus, BMAT is functionally distinct from WAT and BAT. However, in humans basal glucose uptake in BMAT is greater than in axial bones or subcutaneous WAT and can be greater than that in skeletal muscle, underscoring the potential of BMAT to influence systemic glucose homeostasis. These PET/CT studies characterise BMAT function in vivo, establish new methods for BMAT analysis, and identify BMAT as a distinct, major adipose tissue subtype.

The purpose of this study was to measure the errors introduced by regular calibration of PET/CT scanners and to minimize the effect of calibration error on standardized uptake value measurements. Methods Global calibration factors from 2 PET/CT scanners were recorded for 3.5 and 1.8 y, comparing manufacturer-recommended protocols with modified protocols to evaluate error contributions due to operator-influenced procedures. Dose calibrator measurements were evaluated using National Institute of Standards and Technology–traceable sources. Results Dose calibrator variability was less than 1%, although there was a consistent bias. Global scaling variability was reduced from 6% to 4% for scanner 1 and from 11% to 4% for scanner 2 when quality assurance and quality control procedures were applied to the calibration protocol. When calibrations were done using a 68Ge/68Ga phantom, the variability for both scanners was reduced to approximately 3%. Conclusion Applying quality assurance and quality control procedures to scanner calibration reduces variability, but there is a still a residual longitudinal scanner variability of 3%–4%. The procedures proposed here reduce the impact of operator error on scanner calibration and thereby minimize longitudinal variability in standarized uptake value measurements.

Continuous miniature crystal element (cMiCE) detectors are a potentially lower cost alternative for high resolution discrete crystal PET detector designs. We report on performance characteristics of a prototype PET scanner consisting of two cMiCE detector modules. Each cMiCE detector is comprised of a 50 × 50 × 8 mm3 LYSO crystal coupled to a 64 channel multi-anode PMT. The cMiCE detectors use a statistics-based positioning method based upon maximum likelihood estimation for event positioning. By this method, cMiCE detectors can also provide some depth of interaction event positioning information. For the prototype scanner, the cMiCE detectors were positioned across from one another on a horizontal gantry with a detector spacing of 10.7 cm. Full tomographic data were collected and reconstructed using single slice rebinning and filtered back projection with no smoothing. The average image resolutions in X (radial), Y (transverse) and Z (axial) were 1.05 ± 0.08 mm, 0.99 ± 0.07 mm, 1.24 ± 0.31 mm FWHM. These initial imaging results from a prototype imaging system demonstrate the outstanding image resolution performance that can be achieved using the potentially lower cost cMiCE detectors.

Preclinical PET/CT is a well-established noninvasive imaging tool for studying disease development/progression and the development of novel radiotracers and pharmaceuticals for clinical applications. Despite this pivotal role, standardization of preclinical PET/CT protocols, including CT absorbed dose guidelines, is essentially nonexistent. This study (1) quantitatively assesses the variability of current preclinical PET/CT acquisition and reconstruction protocols routinely used across multiple centers and scanners; and (2) proposes acquisition and reconstruction PET/CT protocols for standardization of multicenter data, optimized for routine scanning in the preclinical PET/CT laboratory. Methods: Five different commercial preclinical PET/CT scanners in Europe and the United States were enrolled. Seven different PET/CT phantoms were used for evaluating biases on default/general scanner protocols, followed by developing standardized protocols. PET, CT, and absorbed dose biases were assessed. Results: Site default CT protocols were the following: greatest extracted Hounsfield units (HU) were 133 HU for water and −967 HU for air; significant differences in all tissue equivalent material (TEM) groups were measured. The average CT absorbed doses for mouse and rat were 72 mGy and 40 mGy, respectively. Standardized CT protocol were the following: greatest extracted HU were −77 HU for water and −990 HU for air; TEM precision improved with a reduction in variability for each tissue group. The average CT absorbed dose for mouse and rat decreased to 37 mGy and 24 mGy, respectively. Site default PET protocols were the following: uniformity was substandard in one scanner, recovery coefficients (RCs) were either over-or underestimated (maximum of 43%), standard uptake values (SUVs) were biased by a maximum of 44%. Standardized PET protocols were the following: scanner with substandard uniformity improved by 36%, RC variability decreased by 13% points, and SUV accuracy improved to 10%. Conclusion: Data revealed important quantitative biases in preclinical PET/CT and absorbed doses with default protocols. Standardized protocols showed improvements in measured PET/CT accuracy and precision with reduced CT absorbed dose across sites. Adhering to standardized protocols generates reproducible and consistent preclinical imaging datasets, thus augmenting translation of research findings to the clinic.

Our laboratory has been developing a depth-of-interaction (DOI) detector design based on light sharing between pairs or quadlets of crystals. Work to date has been utilizing 2×2 mm cross section crystals carefully positioned on a multi-anode PMT. However, there is still significant light sharing in the PMT glass envelope and current PMT designs do not allow one-on-one coupling for arrays of smaller cross section crystals. One-on-one coupling is optimal for implementing the DOI estimator. An alternative to PMTs is to take advantage of progress in fabrication of metal resistive-layer semiconductor photodetectors to provide arrays with one-on-one crystal coupling. We report on our initial tests of one manufacturer's devices. The photodetector (MAPD) and scintillator combination (LFS-3) are both products of Zecotek. The LFS-3 crystal is a variant of LFS that has a better spectral match to the MAPD. Measurements show performance equivalent to or better than that obtained with PMTs and LSO, LFS, or LYSO crystals. For example, 2×2×20 mm crystals are providing 11% energy resolution. The high gain of such devices allow flexibility in designs for both the array and the supporting electronics. We are proceeding with the dMiCE development based on the use of MAPD and LFS-3 arrays.

Modern Field Programmable Gate Arrays (FPGAs) are capable of performing complex discrete signal processing algorithms with clock rates above 100MHz. This combined with FPGA’s low expense, ease of use, and selected dedicated hardware make them an ideal technology for a data acquisition system for positron emission tomography (PET) scanners. Our laboratory is producing a high-resolution, small-animal PET scanner that utilizes FPGAs as the core of the front-end electronics. For this next generation scanner, functions that are typically performed in dedicated circuits, or offline, are being migrated to the FPGA. This will not only simplify the electronics, but the features of modern FPGAs can be utilizes to add significant signal processing power to produce higher resolution images. In this paper two such processes, sub-clock rate pulse timing and event localization, will be discussed in detail. We show that timing performed in the FPGA can achieve a resolution that is suitable for small-animal scanners, and will outperform the analog version given a low enough sampling period for the ADC. We will also show that the position of events in the scanner can be determined in real time using a statistical positioning based algorithm.

We have previously reported on dMiCE, a method of resolving depth or interaction (DOI) in a pair of discrete crystals by encoding light sharing properties as a function of depth in the interface of a crystal-element pair. A challenge for this method is the cost and repeatability of interface treatment for each crystal pair. In this work, we report our preliminary results on using sub-surface laser engraving (SSLE) as a means of forming this depth-dependent interface in a dMiCE detector. A surplus first-generation SSLE system was used to create a partially reflective layer 100-microns thick at the boundary between two halves of a 1.4-by-2.9-by-20 mm3 LYSO crystal. The boundary of these paired crystal elements was positioned between two 3-mm wide Silicon photomultiplier arrays. The responses of these two photodetectors were acquired for an ensemble of 511-keV photons collimated to interact at a fixed depth in just one crystal element. Interaction position was then varied to measure detector response as a function of depth, which was then used to maximum-likelihood positions. Despite use of sub-optimal SSLE processing we found an average DOI resolution of 3.4 mm for front-sided readout and 3.9 mm for back-sided readout while obtaining energy resolutions on the order of 10%. We expect DOI resolution can be improved significantly by optimizing the SSLE process and pattern.

BackgroundA feasibility study was done to assess the capability of digital silicon photomultipliers to measure the Cherenkov luminescence emitted by a β source. Cherenkov luminescence imaging (CLI) is possible with a charge coupled device (CCD) based technology, but a stand-alone technique for quantitative activity measurements based on Cherenkov luminescence has not yet been developed. Silicon photomultipliers (SiPMs) are photon counting devices with a fast impulse response and can potentially be used to quantify β-emitting radiotracer distributions by CLI.MethodsIn this study, a Philips digital photon counting (PDPC) silicon photomultiplier detector was evaluated for measuring Cherenkov luminescence. The PDPC detector is a matrix of avalanche photodiodes, which were read one at a time in a dark count map (DCM) measurement mode (much like a CCD). This reduces the device active area but allows the information from a single avalanche photodiode to be preserved, which is not possible with analog SiPMs. An algorithm to reject the noisiest photodiodes and to correct the measured count rate for the dark current was developed.ResultsThe results show that, in DCM mode and at (10–13) °C, the PDPC has a dynamic response to different levels of Cherenkov luminescence emitted by a β source and transmitted through an opaque medium. This suggests the potential for this approach to provide quantitative activity measurements. Interestingly, the potential use of the PDPC in DCM mode for direct imaging of Cherenkov luminescence, as a opposed to a scalar measurement device, was also apparent.ConclusionsWe showed that a PDPC tile in DCM mode is able to detect and image a β source through its Cherenkov radiation emission. The detector’s dynamic response to different levels of radiation suggests its potential quantitative capabilities, and the DCM mode allows imaging with a better spatial resolution than the conventional event-triggered mode. Finally, the same acquisition procedure and data processing could be employed also for other low light levels applications, such as bioluminescence.Electronic supplementary materialThe online version of this article (doi:10.1186/s40658-015-0134-z) contains supplementary material, which is available to authorized users.