Development of a PET/EPRI combined imaging system for assessing tumor hypoxia.

Precise quantitative delineation of tumor hypoxia is essential in radiation therapy treatment planning to improve the treatment efficacy by targeting hypoxic sub-volumes. We developed a combined imaging system of positron emission tomography (PET) and electron para-magnetic resonance imaging (EPRI) of molecular oxygen to investigate the accuracy of PET imaging in assessing tumor hypoxia. The PET/EPRI combined imaging system aims to use EPRI to precisely measure the oxygen partial pressure in tissues. This will evaluate the validity of PET hypoxic tumor imaging by (near) simultaneously acquired EPRI as ground truth. The combined imaging system was constructed by integrating a small animal PET scanner (inner ring diameter 62 mm and axial field of view 25.6 mm) and an EPRI subsystem (field strength 25 mT and resonant frequency 700 MHz). The compatibility between the PET and EPRI subsystems were tested with both phantom and animal imaging. Hypoxic imaging on a tumor mouse model using 18F-fluoromisonidazole radio-tracer was conducted with the developed PET/EPRI system. We report the development and initial imaging results obtained from the PET/EPRI combined imaging system.

Design, evaluation and initial imaging results of a PET insert based on strip-line readout for simultaneous PET/MRI.

We present the development of a PET insert system for potential simultaneous PET/MR imaging using a 9.4 T small animal MRI scanner to test our system. The detectors of the system adopt a strip-line based multiplexing readout method for SiPM signals. In this readout, multiple SiPM outputs in a row share a common strip-line. The position information about a hit SiPM is encoded in the propagation time difference of the signals arriving at the two ends of the strip-line. The use of strip-lines allows us to place the data acquisition electronics remotely from the detector module to greatly simplify the design of the detector module and minimize the mutual electromagnetic interference. The prototype is comprised of 14 detector modules, each of which consists of an 8x4 LYSO scintillator array (each LYSO crystal is 3x3x10 mm3) coupled to two units of Hamamatsu MPPC arrays (4x4, 3.2 mm pitch) that are mounted on a strip-line board. On the strip-line board, outputs of the 32 SiPMs are routed to 2 strip-lines so that 16 SiPM signals share a strip-line. The detector modules are installed inside a plastic cylindrical supporting structure with an inner and outer diameter of 60 mm and 115 mm, respectively, to fit inside a Bruker BioSpec 9.4 Tesla MR scanner. The axial field of view of the prototype is 25.4 mm. The strip-lines were extended by using 5-meter cables to a sampling data acquisition (DAQ) board placed outside the magnet. The detectors were not shielded in the interest of investigating how they may affect and be affected by the MRI. Experimental tests were conducted to evaluate detection performance, and phantom and animal imaging were carried out to assess the spatial resolution and the MR compatibility of the PET insert. Initial results are encouraging and demonstrate that the prototype insert PET can potentially be used for PET/MR imaging if appropriate shielding will be implemented for minimizing the mutual interference between the PET and MRI systems.

Note: Rapid measurement of fluorescence lifetimes using SiPM detection and waveform sampling.

In fluorescence spectroscopy and imaging, fluorescence lifetime measurement-assessing the average time fluorophores spend in their excited state before returning to their ground state-offers a number of advantages over quantifying fluorescence intensities that include resistance to photo-bleaching and independence from fluorophore concentration, excitation intensity, and measurement methodology. Despite growing interest, fluorescence lifetime techniques frequently mandate relatively complex instrumentation, slow data acquisition rates, and significant data analyses. In this work, we demonstrate the feasibility of measuring fluorescence lifetimes using off-the-shelf analog silicon photomultipliers and switched-capacitor array waveform sampling techniques, with precision matching that of much larger and more elaborate commercial instruments.

A Silicon Photo-multiplier Signal Readout Using Strip-line and Waveform Sampling for Positron Emission Tomography.

A strip-line and waveform sampling based readout is a signal multiplexing method that can efficiently reduce the readout channels while fully exploiting the fast time characteristics of photo-detectors such as the SiPM. We have applied this readout method for SiPM-based time-of-flight (TOF) positron emission tomography (PET) detectors. We have prototyped strip-line boards in which 8 SiPMs (pitch 5.2 mm) are connected by using a single strip-line, and the signals appearing at the ends of the strip-line are acquired by using the DRS4 waveform sampler at a nominal sampling frequency of 1-5 GS/s. Experimental tests using laser and LYSO scintillator are carried out to assess the performance of the strip-line board. Each SiPM position, which is inferred from the arrival time difference of the two signals at the ends of the strip-line, is well identified with 2.6 mm FWHM resolution when the SiPMs are coupled to LYSO crystals and irradiated by a 22Na source. The average energy and coincidence time resolution responding to 511 keV photons are measured to be ~32% and ~510 ps FWHM, respectively, at a 5.0 GS/s DRS4 sampling rate. The results show that the sampling rate can be lowered to 1.5 GS/s without performance degradation. These encouraging initial test results indicate that the strip-line and waveform sampling readout method is applicable for SiPM-based TOF PET development.

A feasibility study of a PET/MRI insert detector using strip-line and waveform sampling data acquisition.

We are developing a time-of-flight Positron Emission Tomography (PET) detector by using silicon photo-multipliers (SiPM) on a strip-line and high speed waveform sampling data acquisition. In this design, multiple SiPMs are connected on a single strip-line and signal waveforms on the strip-line are sampled at two ends of the strip to reduce readout channels while fully exploiting the fast time response of SiPMs. In addition to the deposited energy and time information, the position of the hit SiPM along the strip-line is determined by the arrival time difference of the waveform. Due to the insensitivity of the SiPMs to magnetic fields and the compact front-end electronics, the detector approach is highly attractive for developing a PET insert system for a magnetic resonance imaging (MRI) scanner to provide simultaneous PET/MR imaging. To investigate the feasibility, experimental tests using prototype detector modules have been conducted inside a 9.4 Tesla small animal MRI scanner (Bruker BioSpec 94/30 imaging spectrometer). On the prototype strip-line board, 16 SiPMs (5.2 mm pitch) are installed on two strip-lines and coupled to 2 × 8 LYSO scintillators (5.0 × 5.0 × 10.0 mm3 with 5.2 mm pitch). The outputs of the strip-line boards are connected to a Domino-Ring-Sampler (DRS4) evaluation board for waveform sampling. Preliminary experimental results show that the effect of interference on the MRI image due to the PET detector is negligible and that PET detector performance is comparable with the results measured outside the MRI scanner.

A New Time Calibration Method for Switched-capacitor-array-based Waveform Samplers.

We have developed a new time calibration method for the DRS4 waveform sampler that enables us to precisely measure the non-uniform sampling interval inherent in the switched-capacitor cells of the DRS4. The method uses the proportionality between the differential amplitude and sampling interval of adjacent switched-capacitor cells responding to a sawtooth-shape pulse. In the experiment, a sawtooth-shape pulse with a 40 ns period generated by a Tektronix AWG7102 is fed to a DRS4 evaluation board for calibrating the sampling intervals of all 1024 cells individually. The electronic time resolution of the DRS4 evaluation board with the new time calibration is measured to be ~2.4 ps RMS by using two simultaneous Gaussian pulses with 2.35 ns full-width at half-maximum and applying a Gaussian fit. The time resolution dependencies on the time difference with the new time calibration are measured and compared to results obtained by another method. The new method could be applicable for other switched-capacitor-array technology-based waveform samplers for precise time calibration.

An Application of Micro-channel Plate Photomultiplier Tube to Positron Emission Tomography.

We are developing a Time-of-Flight Positron Emission Tomography detector using flat panel micro-channel plate photomultiplier tubes (MCP PMT). The high-speed waveform sampling data acquisition is adopted to exploit the fast time response of MCP PMT efficiently by using transmission-line readout scheme. To demonstrate the feasibility of the proposed detector, prototype detector modules were built using Photonis XP85022 MCP PMT, transmission-line board (TL), and high-speed waveform sampling electronics equipped with DRS4 chips. The MCP/TL module was coupled to single LYSO crystal, and experimental tests have been conducted in a coincidence setup to measure the responses to 511 keV annihilation photon. The details of the prototype module, experimental setup, and the preliminary results are presented and discussed.

A Prototype TOF PET Detector Module Using a Micro-Channel Plate Photomultiplier Tube with Waveform Sampling.

We are exploring a large area flat panel micro-channel plate photomultiplier tube (MCP PMT) under development for an application to time-of-flight positron emission tomography (TOF PET). High speed waveform sampling with transmission-lines is adopted for reading out the signal with precise time and space information with a small number of low-power channels. As a demonstration of the concept, detector modules have been built using 2″×2″ Photonis Planacon MCP PMTs (XP85022) and prototype transmission-line (TL) boards. The signals from the MCP PMT through the transmission-lines are sampled by DRS4 evaluation boards running at 5 giga-samples per second (GS/s). The event information is extracted by processing the digitized waveforms. For experimental tests, a single 3×3×10 mm(3) LYSO crystal is optically coupled to each MCP PMT; the detector responses to 511 keV annihilation photon from a (22)Na source are measured using the data taken in coincidence mode. As a preliminary result, we obtain a position resolution of ∼2.8 mm (0.3 mm) (FWHM) along (perpendicular to) the transmission-line, ∼309 ps (FWHM) for coincidence time resolution, and ∼14% (FWHM) of energy resolution at 511 keV. This initial result gives a promise that the large area MCP PMT is applicable to TOF PET.

A Design of a PET Detector Using Micro-Channel Plate Photomultipliers with Transmission-Line Readout.

A computer simulation study has been conducted to investigate the feasibility of a positron emission tomography (PET) detector design by using micro-channel plate (MCP) photomultiplier tubes (PMT) with transmission-line (TL) read-out and waveform sampling. The detector unit consisted of a 24×24 array of pixelated LSO crystals, each of which was 4×4×25 mm(3) in size, and two 102×102 mm(2) MCP-PMTs coupled to both sides of the scintillator array. The crystal (and TL) pitch was 4.25 mm and reflective medium was inserted between the crystals. The transport of the optical photons inside the scintillator were simulated by using the Geant4 package. The output pulses of the MCP-PMT/TL unit were formed by applying the measured single photo-electron response of the MCP-PMT/TL unit to each individual photon that interacts with the photo-cathode of the MCP-PMT. The waveforms of the pulses at both ends of the TL strips were measured and analyzed to produce energy and timing information for the detected event. An experimental setup was developed by employing a Photonis Planacon MCP-PMT (XP85022) and a prototype TL board for measuring the single photo-electron response of the MCP-PMT/TL. The simulation was validated by comparing the predicted output pulses to measurements obtained with a single MCP-PMT/TL coupled to an LSO crystal exposed to 511 keV gamma rays. The validated simulation was then used to investigate the performance of the proposed new detector design. Our simulation result indicates an energy resolution of ~11% at 511 keV. When using a 400-600 keV energy window, we obtain a coincidence timing resolution of ~323 ps FWHM and a coincidence detection efficiency of ~40% for normally-incident 511keV photons. For the positioning accuracy, it is determined by the pitch of the TLs (and crystals) in the direction normal to the TLs and measured to be ~2.5 mm in the direction parallel to the TLs. The energy and timing obtained at the front- and back-end of the scintillator array also show differences that are correlated with the depth of interaction of the event.

Dissociation of heme from gaseous myoglobin ions studied by infrared multiphoton dissociation spectroscopy and Fourier-transform ion cyclotron resonance mass spectrometry.

Detachment of heme prosthetic groups from gaseous myoglobin ions has been studied by collision-induced dissociation and infrared multiphoton dissociation in combination with Fourier-transform ion cyclotron resonance mass spectrometry. Multiply charged holomyoglobin ions (hMbn+) were generated by electrospray ionization and transferred to an ion cyclotron resonance cell, where the ions of interest were isolated and fragmented by either collision with Ar atoms or irradiation with 3 mum photons, producing apomyoglobin ions (aMbn+). Both charged heme loss (with [Fe(III)-heme]+ and aMb(n-1)+ as the products) and neutral heme loss (with [Fe(II)-heme] and aMbn+ as the products) were detected concurrently for hMbn+ produced from a myoglobin solution pretreated with reducing reagents. By reference to Ea = 0.9 eV determined by blackbody infrared radiative dissociation for charged heme loss of ferric hMbn+, an activation energy of 1.1 eV was deduced for neutral heme loss of ferrous hMbn+ with n = 9 and 10.