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.

Misinterpretation of body sensations in panic disorder.

Cognitive accounts of panic predict that panic disorder patients will be particularly prone to misinterpret autonomic sensations. Several studies have produced results consistent with this prediction, but each is open to alternative interpretation. To clarify matters, 2 studies administered the Body Sensations Interpretation Questionnaire (BSIQ) to panic patients and controls. Panic patients were more likely to interpret ambiguous autonomic sensations as signs of immediately impending physical or mental disaster and were more likely than other anxiety disorder patients and nonpatients to believe these interpretations. In a 3rd study, a brief version of the BSIQ was shown to have satisfactory test-retest reliability, to change with treatment, and to discriminate treatments that varied in their effects on panic.

Effects of neutralizing on intrusive thoughts: an experiment investigating the etiology of obsessive-compulsive disorder.

A large sample of non-clinical subjects were screened and those who reported experiencing relatively frequent intrusive thoughts with associated neutralizing were selected. These subjects were randomly allocated to one of two conditions: both groups listened to repeated recorded presentations of one of their intrusive thoughts and were then required either to (a) neutralize it, or (b) distract themselves for a similar period. Ratings of discomfort were taken during this procedure (first phase), and during identical presentations of the same thought without neutralizing or distracting (second phase). Results showed that the group who neutralized during the first phase experienced significantly more discomfort during the second phase and significantly stronger urges to neutralize and distract. There was also evidence that engaging in neutralizing responses during the first phase made it difficult to stop neutralizing during the second phase. The results are considered in the context of the cognitive-behavioural hypothesis that obsessional disorders develop as a consequence of neutralizing normal intrusive thoughts.

Microchannel array detector for quantitative electronic radioautography.

The microchannel array detector provides direct electronic detection and real time imaging of radioactive tracers in samples that traditionally have been imaged by film radioautography. The technology of the detector is described, and the main benefits of this new technology, speed and precise quantitation, are illustrated with practical results. The instrument response to a 14C dilution series (range of 10(5)) was linear over the whole range. Results from the microchannel array detector are compared to results obtained with liquid scintillation counting (LSC) and densitometry of film radioautographs. Because the instrument response is linear and consistent from day to day, it is not necessary to routinely include calibration standards as is required for film. The 14C counting efficiency was found to be essentially constant for different tissues in a whole body microtome section. As with LSC, results reported as counts per min. (CPM) are independent of counting time. Quantitative results were obtained with assays for chloramphenicol acetyl transferase in two min. and little as 0.2 DPM/mm2 of 32P was detected in seven min.

High density avalanche chamber (HIDAC) positron camera.

A prototype positron camera has been constructed consisting of two high density avalanche chamber (HIDAC) detectors operated in coincidence with a resolving time (2 tau) of 40 nsec. The detectors are multiwire chambers, with specially constructed lead converters added to improve the photon detection efficiency at 511 keV. The current HIDAC detectors have a singles efficiency of approximately 12%, a sensitive area of 31 X 31 cm and an intrinsic spatial resolution of less than 2 mm full width at half maximum (FWHM). During data acquisition, the detectors are rotated around the patient in order to collect a complete angular data set. A three-dimensional image of the positron distribution is reconstructed from a single scan by weighted backprojection of the data into a matrix of either 64 X 64 X 64 or 128 X 128 X 16 voxels. The camera point response function is deconvolved by frequency-space filtering. Corrections are made during backprojection both for photon attenuation and for spatial variations in point source sensitivity. The reconstructed image is further corrected for contributions from accidental and scattered coincidences and displayed as a sequence of two-dimensional transverse, sagittal, or coronal sections. In addition, three-dimensional display is available using shaded graphics techniques. The prototype camera is currently undergoing clinical evaluation.

Tomographic imaging of the human thyroid using 124I.

After receiving between 100 and 300 mu Ci of the positron-emitting radioisotope 124I (half-life, 4.2 days), 64 patients with a variety of thyroid disorders were imaged with a high resolution positron camera. A 3-dimensional image of the distribution of radioiodine uptake within the thyroid was obtained from a single 10- to 15-min scan. This image may be viewed as a sequence of 2-mm thick transverse, sagittal, or frontal sections or as a 3-dimensional shaded surface. The functional volume of the thyroid may be estimated by counting the volume elements (voxels) inside the thyroid surface. The precision of the estimate varied from 6-15%, depending on the size and clinical status of the thyroid. The volume estimation procedure was validated with phantoms and with the thyroids of patients who subsequently underwent partial thyroidectomy. This 3-dimensional imaging technique may be useful for diagnosis and management of thyroid diseases.

In vivo imaging of the human thyroid with a positron camera using 124I.

A high-density avalanche chamber (HIDAC) positron camera was used for tomographic imaging of the human thyroid in vivo. Images were made 7 and 24 h after the oral administration of the positron-emitting radionuclide, sodium iodide 124I (with activities varying between 0.3 and 1 mCi), to patients scheduled for either partial thyroidectomy or radioiodine treatment. The results of thyroid imaging performed on 38 patients and their clinical relevance are discussed; as an illustration, three typical cases are presented. In Graves' disease, it was found that, whereas standard 131I and 124I scintigrams showed a diffuse goitre, positron images indicated a marked heterogeneity of the activity distribution, with "cold" areas in 8 out of the 11 cases studied. In conventional scintigrams, multinodular goitre showed a non-uniform radioiodine distribution, while positron images revealed considerable regional differences of activity uptake, with hot and cold areas in all of the 13 cases studied. As a consequence of the high spatial resolution of the camera [2.5 mm full width at half maximum (FWHM)], the functional volume of the thyroid may be estimated from 2 mm-thick transverse tomographic sections to within about 13%. This estimate may be compared with the measured volume after partial thyroidectomy, and in a follow-up scan, a further estimate can be made of the residual thyroid tissue remaining within the patient's body. In the case of radioiodine treatment in Graves' disease and multinodular goitre, the appropriate therapeutic dose of 131I can calculated according to the functional volume of the thyroid estimated from 124I tomographic images.

Tomographic imaging of the human thyroid with a positron camera before and after partial thyroidectomy.

A high-density avalanche chamber positron camera was used for tomographic imaging of the human thyroid before and after partial thyroidectomy. Images were made between 6 and 24 h after oral administration of the positron-emitting radionuclide, Na-124I with activities varying between 0.1 and 0.3 mCi before the surgical intervention and with activities between 0.03 and 0.05 mCi following partial thyroidectomy. The results of thyroid imaging performed on 50 patients and their surgical relevance are discussed; as an illustration, one typical case is presented. As a consequence of the high spatial resolution of the camera (2.5 mm full width at half maximum), the functional volume of the thyroid may be estimated from the transaxial tomographic sections before and following partial thyroidectomy, correct to about 10%. The thyroid surface, defined by the contours from each transaxial section, may be displayed using three-dimensional shaded-graphics techniques. This new imaging technique makes possible a fully three-dimensional description of the thyroid in vivo and contributes significantly to the surgical follow-up.

Object reconstruction from focused positron tomograms.

A major problem with the reconstruction of three-dimensional object distributions from focused tomographic images using Fourier transforms is the amplification of statistical noise in certain frequency components. This paper describes the use of a generalised matrix inversion technique to limit noise amplification to a level related to the spatial resolution of the imaging system. The reconstruction method is applied to a simulated positron camera, and results are presented on the imaging of an extended, three-dimensional object distribution. A significant improvement in the elimination of the background is achieved.