Stephen McCallum

Attenuation correction in PET using consistency conditions and a three-dimensional template

Attenuation correction is required in positron emission tomography for accurate quantitation and to reduce artifacts. In previous work, the authors have shown that consistency information can be used to perform attenuation correction in the absence of any transmission measurements. In the previous work, a separate object was used for each slice and was transformed in two dimensions. Here, the authors introduce an extension that performs three-dimensional transformations on a single object over many slices. The aim is to produce a useful attenuation correction in situations where either it is impractical to acquire transmission data or there is significant misregistration between the transmission and emission data. Results are presented for simulated test cases with uniform and nonuniform attenuation and experimental cardiac phantom data. The algorithm as it stands is too unstable to allow for accurate attenuation correction without any transmission measurements. However, it may be useful for correcting misregistration, and may possibly be extended to perform coregistration.

In vivo detection of a pH‐sensitive nitroxide in the rat stomach by low‐field ESR‐based techniques

A study was made of the in vivo detectability of a pH‐sensitive, imidazolidine spin probe, and the efficacy of low‐frequency electron spin resonance (ESR)‐based techniques for pH measurement in vitro and in vivo in rats. The techniques used were longitudinally‐detected ESR (LODESR) and field‐cycled dynamic nuclear polarization (FC‐DNP) for in vitro and in vivo measurements, and radiofrequency (RF)‐ and X‐band ESR for comparisons in vitro. The spin probe was hexamethyl imidazolidine (HMI) with a pK of 4.6. All techniques detected HMI. Detection by FC‐DNP implies coupling between the free radical and solvent water spins. Separations between the three spectral lines of the nitroxide radical, relative to measurement frequency, were consistent with theory. The overall spectrum width from unprotonated HMI (pH > pK) was greater than that from protonated agent (pH < pK). This was observed in vitro and in vivo. Longer‐term studies showed that HMI is detectable and has the same spectral width (i.e., is at the same pH) up to 2 hr after gavage into the stomach, although the magnitude of the signal decreases rapidly during the first hour. These findings demonstrate the suitability of LODESR and FC‐DNP for monitoring HMI and measuring pH in vivo. These techniques would be useful for monitoring disease and drug pharmacology in the living system. Magn Reson Med 49:558–567, 2003.

A four-layer attenuation compensated PET detector based on APD arrays without discrete crystal elements

Scintillation detectors developed for PET traditionally use relatively thick crystals coupled to photomultiplier tubes. To ensure good efficiency the crystals typically measure between 10 and 30 mm thick. Detectors also require good spatial resolution so the scintillator is normally made up of a densely packed array of long thin crystals. In this paper, we present a novel design in which the detection crystal is divided into a number of layers along its length with an avalanche photo diode (APD) inserted between each layer. With thin layers of crystal, it is possible to use a continuous rather than a pixelated crystal. The potential advantages of this design over a conventional PMT-based detector are: (i) improved light collection efficiency, (ii) reduced dependency on dense crystal to achieve good stopping power, (iii) ease of crystal manufacture, (iv) reduced detector dead-time and increased count rate, and (v) inherent depth of interaction. We have built a four-layer detector to test this design concept using Hamamatsu S8550 APD arrays and LYSO crystals. We used the centre 16 pixels of each of the arrays to give an active area of 9.5 mm x 9.5 mm. Four crystals 9.5 mm x 9.5 mm were used with thickness increasing from 2 mm at the front to 2.5 mm, 3.1 mm and 4.3 mm at the back, to ensure a similar count rate in each layer. Calculations for the thickness of the four layers were initially made using the linear attenuation coefficient for photons at 511 keV of LYSO. Experimental results and further simulation demonstrated that a correction to the thickness of each layer should be considered to take into account the scattered events. The energy resolution for each of the layers at 511 keV was around 15%, coincidence-timing resolution was 2.2 ns and the special resolution was less than 2 mm using a statistical-based positioning algorithm.

Nitroxide free radical clearance in the live rat monitored by radio-frequency CW-EPR and PEDRI

The use of RF (100 to 300 MHz) PEDRI and CW-EPR techniques allows the in vivo study of large animals such as whole rats and rabbits. Recently a PEDRI instrument was modified to also allow CW-EPR spectroscopy with samples of similar size and under the same experimental conditions. In the present study, this CW-EPR and PEDRI apparatus was used to assess the feasibility of the detection of a pyrrolidine nitroxide free radical (2,2,5,5,-tetramethylpyrrolidine-1-oxyl-3-carboxylic acid, PCA) in the abdomen of rats. In particular, we have shown that after the PCA administration (4 mmol kg(-1) b.w.): (i) the PCA EPR linewidth does not show line broadening due to concentration effects; (ii) a similar PCA up-take phase is observed by EPR and PEDRI; and (iii) the PCA half-lives in the whole abdomen of rats measured with the CW-EPR (T1/2=26+/-4 min, mean+/-sd, n=10) and PEDRI (T1/2=29+/-4 min, mean+/-sd, n=4) techniques were not significantly different (p > 0.05). These results show, for the first time, that information about PCA pharmacokinetics obtained by CW-EPR is the same as that from PEDRI under the same experimental conditions.

Recent developments in combining LODESR imaging with proton NMR imaging

We have designed and constructed RF coil assemblies and the appropriate instrumentation for combining proton NMR imaging with LODESR imaging. This has enabled us to collect sequential images from the same sample using both methods. The coil assembly consists of a crossed ellipse coil for LODESR and proton NMR signal detection and a saddle coil for excitation of the ESR resonance. Images have been collected of phantoms containing copper sulphate and Tempol solutions. NMR images were collected (4.3 min) and within 30 s LODESR data collection started (collection time 2.5 min). Only the Tempol solutions are visible in the LODESR images.

Automatic coupling control system for radio frequency in vivo electron paramagnetic resonance based on a piezoelectric controlled capacitor

Electron paramagnetic resonance (EPR) experiments on whole animals present a number of challenging problems. With the animal placed inside the resonant structure, respiratory and cardiac motion cause the resonant frequency and coupling to change dynamically. We have developed an automatic coupling control (ACC) system designed to reduce motion artifacts using an electronically controlled variable capacitor based on a piezoelectric actuator. The capacitor is varied between 11 and 21 pF. We have also developed a novel method for detecting coupling mismatches. The ACC system operates by applying a small modulation signal to the piezo-capacitor control voltage, which in turn modulates the coupling and the reflected signal from the resonator. The phase of the modulation signal, at the output of the diode detector, depends on whether the resonator is under- or overcoupled. We have tested the system with a phantom designed to simulate respiratory motion. The results reported here show that the use of the ACC sys...

Modification of a whole-body NMR imager into a radio frequency EPR spectrometer suitable for in vivo measurements

We report the modification of a low-field whole-body NMR imager to allow radio frequency EPR spectroscopy. The instrument is designed to give optimum sensitivity for in vivo detection of free radicals. The RF circuit is able to operate over a wide frequency range (240 - 320 MHz) and is designed to handle input power levels of up to 12.5 W. The EPR resonator is of the loop - gap type suitable for samples up to 400 ml. A remote resonator coupling method has been developed enabling convenient matching adjustment. An automatic frequency control circuit is able to adjust for frequency deviations caused by animal motion. Where possible, existing imager hardware and commercially available instruments have been used. The instrument is controlled from a central computer via an IEEE 488 instrumentation bus. Here we present sensitivity measurements obtained from a variety of large aqueous samples containing nitroxide free radicals. We show that the instrument is suitable for the detection of exogenous free radicals in 200 g rats.

Multimodality magnetic resonance systems for studying free radicals in vivo

The multimodality approach to in vivo detection of free radicals combines the relative benefits of three free radical detection modalities: conventional RF CW-ESR, LODESR and PEDRI. We have built apparatus capable of combining these modalities to allow sequential PEDRI and CW-ESR, sequential LODESR and proton NMR imaging and simultaneous LODESR and CW-ESR. These systems offer superior performance in terms of both the scope and quality of information over single-modality free radical detection systems.

Continuous-wave NMR imaging of solids.

Current pulsed nuclear magnetic resonance methods of imaging samples such as solids with short spin-spin relaxation times are restricted to use with T2 values longer than approximately 10 µs. In the present study a method of imaging ultra-short T2 samples using continuous-wave, swept-field NMR is presented that, in principle, will be able to overcome this restriction. The technique is identical to that used in continuous-wave electron paramagnetic resonance imaging of paramagnetic species and involves irradiating the sample continuously with a radiofrequency excitation in the presence of a strong stationary magnetic field gradient. When the main magnetic field is swept over a suitable range, the variation of the NMR absorption signal with applied magnetic field yields a one-dimensional projection of the object under study along the gradient direction. Two- or three-dimensional image data sets may be reconstructed from projections that are obtained by applying the gradient in different directions. Signal-to-noise ratio can be improved by modulating the magnetic field and employing a lock-in amplifier to recover signal variations at the audio modulation frequency. Preliminary experiments were performed using a 7 Tesla magnet and a 300 MHz continuous-wave radiofrequency bridge with lock-in detection. The apparatus is described and the results of pilot experiments that employed vulcanized rubber samples are presented. The ability of the technique to detect short T2 samples was demonstrated by the presence of a background signal from the Perspex former of the birdcage resonator used for signal reception.

Simulation of the output from a scintillator/photodiode detector using Monte Carlo techniques and spice circuit simulation

We have developed a procedure to predict the output signal and system noise of various scintillator/photodiode detector combinations. The simulation is in three parts: 1. Monte Carlo techniques are used to model gamma ray interaction and light production in a scintillator 2. The current pulse generated from this light is then modeled, and finally 3. The simulation of photodiode and charge sensitive amplifier response and noise levels are made using a standard Spice package. To validate this procedure we have performed a series of simulations with a variety of scintillators and photodiodes. We have also built detectors in the laboratory to compare results simulated and measured results. Comparisons show good correlation between measured and simulated figures. Now this procedure has been developed and tested it will allow us to test and optimize scintillation detector designs quickly and efficiently.