High accuracy multiple scatter modelling for 3D whole body PET.

A new technique for modelling multiple-order Compton scatter which uses the absolute probabilities relating the image space to the projection space in 3D whole body PET is presented. The details considered in this work give a valuable insight into the scatter problem, particularly for multiple scatter. Such modelling is advantageous for large attenuating media where scatter is a dominant component of the measured data, and where multiple scatter may dominate the total scatter depending on the energy threshold and object size. The model offers distinct features setting it apart from previous research: (1) specification of the scatter distribution for each voxel based on the transmission data, the physics of Compton scattering and the specification of a given PET system; (2) independence from the true activity distribution; (3) in principle no scaling or iterative process is required to find the distribution; (4) explicit multiple scatter modelling; (5) no scatter subtraction or addition to the forward model when included in the system matrix used with statistical image reconstruction methods; (6) adaptability to many different scatter compensation methods from simple and fast to more sophisticated and therefore slower methods; (7) accuracy equivalent to that of a Monte Carlo model. The scatter model has been validated using Monte Carlo simulation (SimSET).

A three-dimensional second-derivative surface-detection algorithm for volume determination on SPECT images.

Most existing techniques for determining volumes on single-photon-emission computed tomography (SPECT) data employ thresholding, two-dimensional edge detection, or manual delineation of edges. These methods, however, are limited in both accuracy and applicability. In seeking to overcome these limitations, a truly three-dimensional (3D) second-derivative-based algorithm which can be implemented with relative ease has been developed. The method incorporates 3D matrix operators; these are convoluted with the SPECT count data in order to produce a 3D voxel map whose data elements correspond to the second derivative of counts in the image. This map is then searched, a suitable derivative-based edge-defining criterion being applied to each voxel position, in order to locate the derivative surface boundary which defines the volume. Validation is obtained using phantom data from 99Tcm-filled bottles of volumes 200, 580 and 2500 cm3 placed within a body-sized tank containing background activities set to give a range of contrasts between 1.00 and 0.75 (i.e. background 0% to 25%). The performance of the algorithm is encouraging: the volumes of the two larger bottles are determined to within a 3% accuracy without the need for any prior calibration, and the results obtained over all bottle sizes are found to be contrast independent to within approximately 4%.

Performance of a block detector PET scanner in imaging non-pure positron emitters--modelling and experimental validation with 124I.

The key performance measures of resolution, count rate, sensitivity and scatter fraction are predicted for a dedicated BGO block detector patient PET scanner (GE Advance) in 2D mode for imaging with the non-pure positron-emitting radionuclides 124I, 55Co, 61Cu, 62Cu, 64Cu and 76Br. Model calculations including parameters of the scanner, decay characteristics of the radionuclides and measured parameters in imaging the pure positron-emitter 18F are used to predict performance according to the National Electrical Manufacturers Association (NEMA) NU 2-1994 criteria. Predictions are tested with measurements made using 124I and show that, in comparison with 18F, resolution degrades by 1.2 mm radially and tangentially throughout the field-of-view (prediction: 1.2 mm), count-rate performance reduces considerably and in close accordance with calculations, sensitivity decreases to 23.4% of that with 18F (prediction: 22.9%) and measured scatter fraction increases from 10.0% to 14.5% (prediction: 14.7%). Model predictions are expected to be equally accurate for other radionuclides and may be extended to similar scanners. Although performance is worse with 124I than 18F, imaging is not precluded in 2D mode. The viability of 124I imaging and performance in a clinical context compared with 18F is illustrated with images of a patient with recurrent thyroid cancer acquired using both [124I]-sodium iodide and [18F]-2-fluoro-2-deoxyglucose.

Evaluation of myocardial thallium tomography in patients with chest pain.

Thirty-seven patients with chest pain have been studied by exercise thallium tomography and coronary arteriography to assess the accuracy of thallium tomography in the identification of patients with coronary artery disease and to evaluate whether knowledge of clinical data improves this accuracy. Thallium tomography was also used to identify which coronary arteries were stenosed. Thallium tomography when compared with coronary arteriography has a sensitivity of 97%, a specificity of 75%, and an overall accuracy of 92% for the detection of coronary artery disease. When clinical information was made available, these results improved to a sensitivity of 100%, a specificity of 75%, and an overall accuracy of 95%. In the identification of which coronary arteries were stenosed, thallium tomography had a sensitivity of 85%, a specificity of 89%, and an overall accuracy of 86%. These results show that exercise thallium tomography can be an accurate non-invasive screening test in patients with chest pain thought to be angina.

HIDA scanning in gall-bladder disease.

HIDA labelled with 99Tcm is a new hepatobiliary imaging radiopharmaceutical which is selectively taken up by the liver and excreted into the biliary tree; it has been shown to demonstrate the gall bladder in normal subjects. Using a gamma-camera computer system, dynamic liver scans were performed during the first hour on 97 patients who, on the basis of standard investigations and on the findings at surgery, were divided into six groups as follows. 1. Normal. 2. Hepatocellular disease. 3. Biliary obstruction. 4. Chronic gall-bladder disease. 5. Acute gall-bladder disease. 6. Acute abdomen (not due to gall-bladder disease). Pictures were taken and activity-time curves of "regions of interest" were generated from the computer data. From these the presence or absence of a gall-bladder image was easily determined. The gall bladder was visualized in all normals but in none of the patients with acute gall-bladder disease. In the group with an acute abdomen suggestive of acute gall-bladder disease, but subsequently shown to be otherwise, the gall bladder was visualized in all cases. The gall bladder was not visualized in 42% of hepatocellular disease patients, nor in any of those with biliary obstruction, due to poor uptake or poor secretion of the HIDA. In cases of chronic gall-bladder disease, visualization of the gall bladder corresponded with gall-bladder opacification on the oral cholecystogram; in these cases the HIDA scan offers no advantage over the oral cholecystogram. These results suggest that in cases of "acute abdomen" an absent gall bladder image with a normal hepatogram will strongly support the diagnosis of acute gall-bladder disease, and that visualization of the gall bladder excludes such a diagnosis, making the HIDA scan a useful first-line investigation in these patients.

The effect of phantom wall thickness on volume determination in SPET.

Assessment, using phantoms, of a a three-dimensional, second-derivative, surface-detection algorithm for accurately determining the volumes of structures in single photon emission tomography (SPET) has shown the performance of the algorithm to be highly dependent on phantom wall thickness. With a 30% background activity level, the volume of a 600-cm3 cylinder with wall thickness approximately 0.4 mm was measured to an accuracy of approximately 1%, whereas for an almost identical cylinder with a wall thickness of approximately 3 mm the measured volume was underestimated by about 14%. To further investigate this 'wall-thickness' effect, theoretically generated SPET data have been produced, simulating a set of low-contrast cylindrical phantoms with identical internal dimensions and wall thicknesses ranging from 0 to 6 mm. These image data have demonstrated a 10% reduction in the calculated volume for wall thicknesses as thin as 1 mm. A less acute dependence is also demonstrated for a threshold-based quantitation algorithm, where a wall thickness of 4-5 mm is required to produce an effect of similar magnitude. The underlying cause behind this 'wall-thickness' effect is undoubtedly the perturbation in the count profile across the surface boundary, which results form the cold region of the phantom wall. Thus, phantom wall thickness will have an effect on the performance of most automated quantitation techniques, both two- and three-dimensional, since the majority must incorporate some form of analysis on this count profile.

An assessment of finger doses received by staff while preparing and injecting radiopharmaceuticals.

Good working practice and legal obligation impose a duty on nuclear medicine departments to check syringe activities before administration to a patient. If syringe guards are used to reduce staff exposure while drawing up injections, the guard has to be removed to measure the activity in a conventional reentrant ionization chamber type calibrator. Alternatively, the activity may be checked in a purpose-built syringe calibrator which allows the assay of the activity in the syringe without the need to remove the syringe guard. Finger doses received during the dose preparation and injection are a cause for concern. This study investigated the finger and whole-body doses received when using each of these calibrators, and compared the results with those obtained by an operator who did not measure the dose at all. The results demonstrated that although the finger doses are small, measurement of the syringe activities in a conventional ionization chamber increases the dose by a factor of 2 above that which would occur if no activity measurements were made, whereas the use of the specialized syringe calibrator gave finger doses only marginally above those obtained with no activity measurement.

The effect on diagnostic quality of using dual isotope imaging for 81Krm ventilation and 99Tcm-MAA perfusion lung scanning.

It is the practice in some centres to use dual isotope imaging to reduce imaging times in lung ventilation and perfusion studies with 81Krm gas and 99Tcm-macroaggregated albumin (99Tcm-MAA) by simultaneous acquisition of the two images. The resulting loss of image caused by cross-talk between the two energy windows was investigated using two phantoms, one with cold 99Tcm lesions of varying size and contrast, and the other a uniform field of 81Krm. It was found that, under scatter conditions typical of a patient study, the use of dual isotope acquisition and a krypton generator of 470 MBq or greater resulted in a perceptible loss of image quality with lesions up to 4 cm in diameter being missed. On an older camera system, without modern energy and linearity correction facilities, a lower generator activity of only 120 MBq was sufficient to cause image degradation even under very low scatter conditions. Seventy-five patient studies were performed using both single and dual isotope imaging with generator activities ranging from 80 to 282 MBq. At these low generator activities, the studies did not demonstrate any differences between the images that would result in a different diagnosis. We conclude that the use of dual isotope V/Q scanning reduces the diagnostic value of the perfusion image if the activity of the 81Krm generator is too high, although at generator activities of 300 MBq or less no loss of image quality will occur on modern camera systems.

The diagnostic value of positron emission tomography (PET) with radiolabelled fluorodeoxyglucose (18F-FDG) in head and neck cancer.

Positron emission tomography (PET) scanning has recently been introduced into clinical practice but its usefulness in the management of head and neck cancer is not well defined. The aim of this prospective preliminary study was to examine the clinical value of fluorodeoxyglucose (FDG)--PET in patients with head and neck cancer treated by radiotherapy with surgery in reserve by (i) relating quantitative uptake of isotope to tumour type and histological grade and (ii) comparing the imaging findings of PET and magnetic resonance imaging (MRI) in post-radiotherapy assessment of tumour response. Twenty-one patients had pre-treatment PET and MRI scans and these were repeated four and eight months after treatment if there was no clinical relapse. Pre-treatment uptake of FDG using tumour to cerebellar ratio parameters was significantly related to the histological grade of squamous cancer (p = 0.04) but not to tumour type. Discordance of post-treatment PET/MRI findings in one case indicates a possible role for PET in the early detection of tumour recurrence. Other potential uses of PET scanning in the management of head and neck cancer are discussed.

Cortical activations in sequential bilateral cochlear implant users.

This study aimed to examine auditory and visual cortical activations in bilateral cochlear implant recipients using [(18)F]-FDG positron emission tomography. We aimed to compare the activations from use of the first implant alone, the second implant alone, and both implants together. When both implants were activated simultaneously, summation of cortical activity did not occur. The first and second implants demonstrated evidence of developing distinct neural networks. The first implants show stronger bilateral recruitment of the auditory areas than the second implants. Visual cortical activations occur in response to stimulation of the second but not the first implants. When both implants were activated together, there were no visual activations suggesting interaction between the first- and second-implant networks. These findings add to the existing knowledge of plasticity following cochlear implantation and demonstrate a variability of these processes that was previously unreported.

Auditory cortical activation and speech perception in cochlear implant users.

Cochlear implantation is generally accepted as a successful means of restoring auditory sensation to profoundly deaf individuals. Although most patients can expect a satisfactory outcome following implantation, some have poor speech perception outcomes. This investigation used [18F]-fluorodeoxyglucose positron emission tomography to measure cortical activity resulting from auditory stimulation in seven 'good' and four 'poor' cochlear implant recipients. Activations were significantly greater in both the primary and association cortices in the good compared with the poor implant users. We suggest that the ability to access the more specialised speech processing abilities of the auditory association cortices helps determine outcome following cochlear implantation.

Should FDG-PET scanning be routinely used for patients with an unknown head and neck squamous primary?

BACKGROUND: Between 1 and 2 per cent of head and neck squamous cell carcinoma patients will reveal no evidence of a primary malignancy. The management of this group poses many problems, including the morbidity associated with wide field irradiation as well as the difficulty in treatment when a primary does emerge. The aim of this study was to assess the use of fluoro-deoxy-glucose positron emission tomography (FDG-PET) imaging in patients presenting with an unknown head and neck primary and to consider its routine use in such patients. METHODS: We enrolled 25 patients into our study over a four year period. They all presented with a histologically proven, metastatic, squamous cell carcinoma of the neck for which no primary could be found despite full clinical, endoscopic and radiological evaluation with computed tomography (CT) and/or magnetic resonance imaging (MRI). Additionally, all the patients underwent imaging using FDG-PET. The images were interpreted by two radiologists experienced in PET imaging. RESULTS: A primary was identified in nine of the 25 patients (42 per cent); however, of these patients, six had false positive results and only three patients were true positives with supportive histology. In the remaining 16 patients, no abnormality was identified on CT, MRI or PET. Of these 16 patients, two eventually displayed a primary carcinoma, the other 14 patients remaining without evidence of any primary. CONCLUSION: Despite the high number of positive PET scans, the actual true positive rate was 3/9 (33 per cent); conversely, the true negative rate was 14/16 (88 per cent). We conclude from this study that there is a role for FDG-PET in the patient with an unknown head and neck primary, particularly in the context of a negative PET scan.

Positron emission tomography of murine liver metastases and the effects of treatment by combretastatin A-4.

There are major potential advantages in non-invasive measurement of preclinical tumour biology and therapeutic response in clinically relevant, internal body sites, notably the ability to follow outcome in individual animals rather than averaging results from groups. We have exploited positron emission tomography (PET) to determine the feasibility of detecting liver metastases in B6D2F1 mice using fluorine-18 fluorodeoxyglucose ([18F]FDG) both before and after treatment by the novel cytotoxic agent, combretastatin A-4. The normal distribution of [18F]FDG in the absence of disease was characterised, with the clear delineation of the brain, the heart and the urinary bladder in all studies. In untreated mice with liver metastases, a strong correlation (r2 = 0.98) was found between the quantitative estimates of [18F]FDG uptake obtained by analysis of PET images, and those obtained from ex vivo assay of liver plus metastases excised immediately after imaging. In this first series, the effective limit of resolution was in livers containing a number of small metastases (range 8-14) with a single volume equivalent of approximately 200 mm3. PET image analysis was concordant with histological measurements in showing that single intraperitoneal doses of combretastatin A-4 resulted in an average 30% volume destruction of metastatic mass by 24 h following administration.

Feasibility of imaging photodynamic injury to tumours by high-resolution positron emission tomography.

One early effect of the treatment of tumours by the new modality photodynamic therapy (PDT) is a reduction in tumour glucose levels. We have employed the widely used positron-emitting glucose analogue flurorine-18 fluoro-2-deoxy-D-glucose ([18F]-FDG), to determine whether, in principle, PDT-induced injury might be delineated non-invasively and quantitatively by positron emission tomography (PET). The scanner was of the high-density avalanche-chamber (HIDAC) type with a resolution of 2.6 mm. Subcutaneous T50/80 mouse mammary tumours, sensitised by haematoporphyrin ester, were illuminated by graded doses of interstitial 630 nm light. Thirty hours later, any remaining viable tumour was detected (a) by region-of-interest analysis of the PET images and (b) by gamma counting the excised tumour. PET measurements of % uptake of [18F]-FDG into tumour correlated closely with ex vivo gamma counting (slope=0.976, r2=0. 995), validating the in situ method. Uptake into untreated, control tumours was 3.8%+/-1.1% of the injected activity. Uptake of [18F]-FDG into treated tumours decreased by 0.7% for every 100 mm3 reduction in remaining viable histological volume. Outcome was further compared with that measured by (a) T2-weighted proton imaging on a 4.7-T magnetic resonance imaging (MRI) system and (b) histological analysis of subsequently sectioned tumours. PET using [18F]-FDG described the absolute volume of surviving tumour histological mass to the same degree as high-resolution MRI. The conclusion of these initial studies is that PET with [18F]-FDG, although non-specific, quantitatively described at early times the extent of tumour destruction by PDT.