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MADPET-II is a novel high-resolution, high-sensitivity three-dimensional lutetium oxyorthosilicate avalanche photodiode small animal PET scanner with a unique detector design and readout that creates new possibilities for data processing and analysis. The scanner consists of a ring of dual-layer detector modules (071 mm), each containing a 4 x 8 array of 2 x 2 x 6[mm.sup.3] (front) and 2 x 2 x 8 [mm.sup.3] (back) LSO crystals that are each optically isolated and coupled one-to-one to a monolithic 4 x 8 APD array. Signals from each channel are individually processed using fully-integrated 16-channel, low noise, charge sensitive preamplifiers and custom integrated electronics that include a four channel shaping amplifier, peak detector and non-delay line CFD. Analog-to-digital converters and time-to-digital converters digitise the pulse height and time-stamp each event, and data are stored exclusively in list mode format. Two 32-channel detector blocks were tested in a coincidence and in a dual-layer configuration. Coincidences were sorted post-acquisition in software, allowing for maximum flexibility in the data processing. Monte Carlo simulations have calculated the system spatial resolution to be 1.1 mm FWHM. Average energy resolution for a single detector block ranged from 20.2 % FWHM to 23.9 % FWHM. System pulse height linearity was measured, and all channels responded with [R.sup.2] > 0.9988 (Pearson correlation coefficient). Intrinsic uniformity for each detector block ranged from 2.0% to 4.8% (400 keV threshold). Overall system timing resolution was measured to be 10.2 ns FWHM, with individual LORs having time resolutions as low as 4.5 ns FWHM. Index Terms--Avalanche photodiode (APD), biomedical nuclear imaging, list mode data, lutetium oxyorthosilicate (LSO), small animal positron emission tomography (PET).

Iterative reconstruction algorithms require prior computation of the system probability matrix P. This matrix is usually estimated from approximated calculations. The approach employed to determine P in this work, however, was based on Monte Carlo simulations. While this technique allows P to be described more accurately, the number of simulated events may limit the statistical quality of P, thus affecting the reconstructed image. The goal of this study was to quantify this effect for OSEM and PWLS applied to the small animal PET system MADPET ([empty set] = 86 mm). System matrices with different statistical quality were obtained by using subsets of the simulated data, and these were then used to reconstruct two simulated phantoms. The results showed that simulations with more than [approximately equal to] 20 000 detected coincidences per pixel barely improved the accuracy of P, but when less than 4 000 detected coincidences per pixel were used, the statistical quality of P deteriorated strongly. PWLS was more sensitive to the inaccurate description of P than OSEM. For PWLS and 1 [mm.sup.2] pixels, any slight increase of the mean relative error for P in the range 23%-30% strongly affected the image properties, while OSEM in combination with any matrix characterized by a mean relative error below [approximately equal to] 40% (obtained from simulations with more than a mean of [approximately equal to] 680 detected counts per pixel) resulted in reasonable images. Good SNR and contrast was assured when using OSEM and a matrix characterized by a mean relative error below 25% (at least 7 000 detected coincidences per pixel). Discarding elements of P that had very small magnitudes reduced the size of the matrix (storage of nonzero elements) and improved the relative error of P and signal-to-noise ratio, especially if OSEM was employed. Index Terms--Iterative reconstruction, Monte Carlo simulations, small animal PET, system probability matrix.

The combination of PET and SPECT in one device may have clinical and economic advantages. The PET/SPECT camera developed as a joint venture between CPS Innovations, Knoxville, TN, and Siemens Medical Systems, Hoffmann Estates, IL, is a fully 3-D system with 511 keV transmission sources. The detector is based on a NaI-LSO phoswich scintillator. The individual LSO and NaI crystals have a size of 4.3 x 4.3 10 [mm.sup.3]. The 12 x 12 crystal blocks are read out by 2 x 2 in photomultiplier tubes, arranged in a low cost quadrant sharing system. The purpose of this paper is to illustrate phoswich detector setup and to evaluate the detector performance for both modes, PET, and SPECT. The quadrant sharing method and the two crystal layers require special algorithms to find the individual crystal regions and distinguish them from light cross talk caused by adjacent blocks. The base for this procedure is a position profile acquired with a flood source. The mean energy resolution for the NaI(TI) crystal layer was 13.1% (FWHM) at 140 keV and 15.7% (FWHM) at 511 keV for the LSO crystal layer. For the PET setup the average time resolution was 3.4 ns (FWHM). A daily quality check showed a very stable detector condition. Peak shifts due to room temperature changes were very little for both modes and both crystal layers. Index Terms--NaI-LSO detector, PET/SPECT, quadrant-sharing.

To take advantage of the compactness of avalanche photodiode (APD) arrays, low-noise power-efficient fast charge-sensitive preamplifier chips with differential current drivers have been developed. A 16-channel and a single-channel version are available. The chips were adapted for low-capacitance 4 x 8 APD arrays produced by Hamamatsu, Japan. A mixed junction field-effect transistor (JFET)-CMOS production process yielded high-quality integrated JFETs for the input stage of the amplifier's folded cascode. Thus, the 1/f-noise corner is kept at 4 kHz. The JFET has a transconductance of 11 mS at a drain current of 3 mA. The serial noise of the input transistor was found to be 0.8 nV/ [square root of Hz]. The signal rise time of the driver outputs is 20 ns. The rms noise of the preamplifier was found to be 480 [e.sup.-] with a 25-[e.sup.-]/pF noise slope for a shaping time of 50 ns. The serial input noise of the preamplifier is about 1.4 nV/ [square root of Hz] from 200 kHz up to 40 MHz, and the 1/f-noise comer is at 70 kHz. The power consumption is 30 mW per preamplifier, including the differential driver. The linearity is better than 1.3% over 48-dB dynamic range. For the 16-channel chip, the channel.to-channel gain variation is less than 3.5%. Performance similar to photo-multiplier tubes can be achieved with APDs in combination with this integrated preamplifier chip. Index Terms--Aavalanche photodiode (APD), charge-sensitive preamplifier, junction field-effect transistor (JTET)-CMOS, low-noise preamplifier.

The advancement of new immunotherapies necessitates appropriate probes to monitor the presence and distribution of distinct immune cell populations. Considering the key role of CD4+ cells in regulating immunological processes, we generated novel single-domain antibodies [nanobodies (Nbs)] that specifically recognize human CD4. After in-depth analysis of their binding properties, recognized epitopes, and effects on T-cell proliferation, activation, and cytokine release, we selected CD4-specific Nbs that did not interfere with crucial T-cell processes in vitro and converted them into immune tracers for noninvasive molecular imaging. By optical imaging, we demonstrated the ability of a high-affinity CD4-Nb to specifically visualize CD4+ cells in vivo using a xenograft model. Furthermore, quantitative high-resolution immune positron emission tomography (immunoPET)/MR of a human CD4 knock-in mouse model showed rapid accumulation of 64Cu-radiolabeled CD4-Nb1 in CD4+ T cell-rich tissues. We propose that the CD4-Nbs presented here could serve as versatile probes for stratifying patients and monitoring individual immune responses during personalized immunotherapy in both cancer and inflammatory diseases. [ABSTRACT FROM AUTHOR]

Invasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of immunocompromised humans, caused by the opportunistic fungal pathogen Aspergillus fumigatus. Inadequacies in current diagnostic procedures mean that early diagnosis of the disease, critical to patient survival, remains a major clinical challenge, and is leading to the empiric use of antifungal drugs and emergence of azole resistance. A non-invasive procedure that allows both unambiguous detection of IPA and its response to azole treatment is therefore needed. Here, we show that a humanised Aspergillus-specific monoclonal antibody, dual labelled with a radionuclide and fluorophore, can be used in immunoPET/MRI in vivo in a neutropenic mouse model and 3D light sheet fluorescence microscopy ex vivo in the infected mouse lungs to quantify early A. fumigatus lung infections and to monitor the efficacy of azole therapy. Our antibody-guided approach reveals that early drug intervention is critical to prevent complete invasion of the lungs by the fungus, and demonstrates the power of molecular imaging as a non-invasive procedure for tracking IPA in vivo. Invasive pulmonary aspergillosis is a life-threatening fungal lung disease devoid of specific rapid diagnosis and with limited therapeutic options. Here, the authors show how state-of-the-art imaging approaches can enable specific diagnosis and therapy monitoring of this infection. [ABSTRACT FROM AUTHOR]

Purpose: Inflammation is involved in many disease processes. However, accurate imaging tools permitting diagnosis and characterization of inflammation are still missing. As inflamed tissues exhibit a high rate of glycolysis, pyruvate metabolism may offer a unique approach to follow the inflammatory response and disease progression. Therefore, the aim of the study was to follow metabolic changes and recruitment of inflammatory cells after onset of inflammation in arthritic ankles using hyperpolarized 1-13C-pyruvate magnetic resonance spectroscopy (MRS) and 19F magnetic resonance imaging (MRI), respectively.Procedure: Experimental rheumatoid arthritis (RA) was induced by intraperitoneal injection of glucose-6-phosphate-isomerase-specific antibodies (GPI) containing serum. To monitor pyruvate metabolism, the transformation of hyperpolarized 1-13C-pyruvate into hyperpolarized 1-13C-lactate was followed using MRS. To track phagocytic immune cell homing, we intravenously injected a perfluorocarbon emulsion 48 h before imaging. The animals were scanned at days 1, 3, or 6 after GPI-serum injection to examine the different stages of arthritic inflammation. Finally, to confirm the pyruvate metabolic activity and the link to inflammatory cell recruitment, we conducted hematoxylin-eosin histopathology and monocarboxylase transporter (MCT-1) immune histochemistry (IHC) of inflamed ankles.Results: Hyperpolarized 1-13C-pyruvate MRS revealed a high rate of lactate production immediately at day 1 after GPI-serum transfer, which remained elevated during the progression of the disease, while 19F-MRI exhibited a gradual recruitment of phagocytic immune cells in arthritic ankles, which correlated well with the course of ankle swelling. Histopathology and IHC revealed that MCT-1 was expressed in regions with inflammatory cell recruitment, confirming the metabolic shift identified in arthritic ankles.Conclusions: Our study demonstrated the presence of a very early metabolic shift in arthritic joints independent of phagocytic immune cell recruitment. Thus, hyperpolarized 1-13C-pyruvate represents a promising tracer to monitor acute arthritic joint inflammation, even with minor ankle swelling. Furthermore, translated to the clinics, these methods add a detailed characterization of disease status and could substantially support patient stratification and therapy monitoring. [ABSTRACT FROM AUTHOR]

Purpose: The development of L-DOPA-induced dyskinesia (LID) is one of the most severe side effects of chronic L-DOPA treatment in Parkinson's disease patients. [11C]DASB positron emission tomography (PET) provides a prominent tool to visualize and quantify serotonin transporter (SERT) pathology in vivo in patients and in animal models. To evaluate the effect of chronic L-DOPA treatment on SERT availability in an animal model of LID, we performed a longitudinal PET study.Procedures: Rats received a unilateral 6-hydroxydopamine (6-OHDA) lesion, and striatal and extrastriatal SERT expression levels were studied with [11C]DASB, a marker of SERT availability, before and after daily treatment with L-DOPA. Dyskinesias were evaluated at different time points over a period of 21 days.Results: [11C]DASB binding was found to be decreased after 6-OHDA lesions in the striatum, cortex, and hippocampus 5 weeks after 6-OHDA injection in the lesioned hemisphere of the rat brain. Chronic L-DOPA priming resulted in a relative preservation of SERT availability in the lesioned and healthy hemisphere compared to baseline measurements.Conclusions: Our longitudinal PET data support a preservation of SERT availability after the induction of L-DOPA-induced dyskinesia, which is in line with previous reports in dyskinetic PD patients. [ABSTRACT FROM AUTHOR]