Single photon emission computed tomography of the brain with Tc-99m HMPAO during sumatriptan challenge in obsessive-compulsive disorder: investigating the functional role of the serotonin auto-receptor.

1. Symptoms of obsessive-compulsive disorder (OCD) may be acutely exacerbated by administration of certain serotonin agonists Exacerbation of OCD symptoms by sumatriptan, a 5HT1D agonist (Zohar, 1993), is consistent with pre-clinical data suggesting that the serotonin auto-receptor plays an important role in this disorder (El Mansari et al, 1995). 2. In order to investigate the functional role of the serotonin auto-receptor in OCD, the authors undertook single photon emission computed tomography in OCD patients after administration of sumatriptan and placebo. The authors hypothesized that, as in the case of m-chlorophenylpiperazine (mCPP) challenge (Hollander et al, 1995), exacerbation of OCD symptoms would be accompanied by increased cortical metabolism and thus blood flow, and more specifically by increased activity in the orbitofrontal-striatal circuit. They also expected, that as in the case of mCPP challenge (Hollander et al, 1993), exacerbation of OCD symptoms would be associated with a relatively poor response to subsequent treatment with serotonin specific reuptake inhibitors. 3. Sumatriptan (100 mg orally) and placebo were administered on separate days to 14 patients who met DSM-IV diagnostic criteria for OCD, using a randomized double-blind design. After 90 minutes, patients were injected with Tc-99m HMPAO and underwent single photon emission computed tomography (SPECT) of the brain. Activity in regions of interest was calculated, and compared using repeated measures analysis of variance. Patients were subsequently treated with a serotonin specific reuptake inhibitor (SSRI). 4. Behavioral response to sumatriptan was heterogenous, with 4 patients showing acute exacerbation, and 4 patients demonstrating a decrease in symptoms. On sumatriptan challenge, there was a significant association between symptom exacerbation and decreased activity in frontal areas. There was an association between decreased activity in an inferior frontal area with worse response to treatment, and also patients with symptom exacerbation after sumatriptan had poorer response to SSRI treatment. 5. Heterogeneity of behavioral response to sumatriptan in OCD is consistent with previous studies demonstrating conflicting and heterogenous behavioral responses to serotonergic challenges (Hollander et al, 1992), and with underlying heterogeneity in the neurobiology of this disorder. 6. It may be hypothesized that increased frontal activity in some patients with OCD is itself a compensatory mechanism. In patients with such compensatory hyperactivity, administration of a serotonin auto-receptor agonist results in decreased frontal activity and exacerbation of OCD symptoms. These patients may also be less likely to respond to treatment with a SSRI. 7. Further work combining pharmacological challenge paradigms and functional imaging techniques in OCD may be helpful in elucidating the neurobiology of this complex disorder.

Quantification of gamma camera spatial resolution by means of bar phantom images.

A method that has previously been described for rapid objective measurement of intrinsic gamma camera spatial resolution using statistical moments has been applied to images of a four-quadrant bar phantom acquired with various collimators. The full-width at half-maximum (FWHM) of the line spread function (LSF) and modulation transfer functions determined by the moments method was compared with those obtained directly from line spread functions. It was found that, for highest accuracy, the formulae originally described for intrinsic measurements have to be modified to take account of a more accurate description of the Fourier components of the input from a bar phantom. When this modification was applied, FWHM measurements agreed to within 4.0% with the LSF measurements in the range 4.5-7.2 mm if well-resolved images of bars wider than 3.0 mm were used. The method is simple to apply and since the coefficient of variation of these measurements was < 2.2%, it is well-suited for rapid objective routine monitoring of gamma camera spatial resolution. For modulation transfer functions > 0.2, bar sizes of 4.0 and 4.5 mm gave values within 4% of the LSF measurements, when the modified formula was applied, with coefficients of variation less than 4%.

Imaging infection and inflammation in an African environment: comparison of 99Tcm-HMPAO-labelled leukocytes and 67Ga-citrate.

A considerable segment of the population of South Africa has a disease spectrum similar to those of the industrialized countries. However, a much larger proportion of its inhabitants comes from historically disadvantaged communities and is plagued by diseases typical of the developing world. Infectious diseases head the list as a cause of mortality in certain age groups. We have studied 108 patients presenting with a wide array of infections. Fifty-eight patients were examined with 67Ga-citrate and with 99Tcm-HMPAO-labelled leukocytes, 40 with leukocytes alone and 10 who had a high pre-test probability of tuberculosis with 67Ga only. The sensitivity and specificity of 99Tcm-labelled leukocyte scintigraphy in the 58 patients who had both studies were 89 and 84%, respectively, while the corresponding values for 67Ga scintigraphy were 81 and 74%, respectively. The overall sensitivity and specificity for 99Tcm-labelled leukocytes for detecting inflammatory sites in all 98 cases were 92 and 89%, respectively. Although labelled leukocytes were the better of the two agents for the early diagnosis of infections with a high probability of neutrophil infiltration, 67Ga remains an excellent alternative. It is the first choice in patients in whom tuberculosis or a neoplastic process is suspected as a cause of fever. It is also safer to use in areas where labelling of leukocytes is inadvisable because of inadequate sterility or where the risk is high of infecting other patients or staff with HIV.

Uniformity testing of a dual-head gamma camera with a nearby point source.

Limitations to head movement of dual-head gamma cameras may prevent proper geometry being attained for testing of intrinsic uniformity with a point source. When a point source is placed too near to the uncollimated crystal, the detected flood image will be non-uniform due to the inverse square law effect, oblique incidence, and increased path length traversed through the crystal by oblique rays. A formula has been deduced for constructing a map to correct for these effects. The general formula has been applied to a particular dual-head camera in which a point source has been placed on the face of one head, at 65.5 cm from the opposite uncollimated crystal. It is shown that division of the non-uniform image, acquired with this geometry, by the correction map yields a uniform image which may be used for routine investigation of the uniformity characteristics of the camera.

Analysis of radiation doses received by the public from 131I treatment of thyrotoxic outpatients.

Radiation doses to the family and general public from 131I therapy of outpatients were assessed for comparison with the 1990 International Commission on Radiation Protection (ICRP) dose limits. Doses to family members of such patients, measured by previous workers, were converted to show that on average 5.6 +/- 3.7 microSv MBq-1 is received by the spouse and 1.5 +/- 0.87 microSv MBq-1 by other family members. It was deduced that the average dose to the spouse (D microSv MBq-1) when couples sleep apart for T days after administration is given by: D = 2.528 + 3.072e-0.11T if an effective half-life, T(eff), of 6.35 days is used. The cumulative effect of repeated treatments should be considered and in view of ALARA it is recommended that couples sleep apart for at least 14 days after each administration, even if this is below limits permitted by authorities. The dose to a pregnant colleague or family member other than the wife should be below 2 mSv if the total administered activity is not more than 600 MBq. If the wife is pregnant, couples should sleep apart for at least 30 days after administration.

Biodistribution of 131I-radiolabelled plasma low density lipoprotein in hyperlipidaemic vervet monkeys.

Low density lipoprotein (LDL) labelled with 131I has been administered to 6 Vervets 2 of which were high responders to an atherogenic Western diet in terms of plasma cholesterol, 2 were low responders and 2 were fed a high carbohydrate control diet. The ratio of hepatic to cardiac activity was recorded for up to 10 days after administration of the labelled LDL. Liver activity had a longer biological half life in the high-responders and this can be interpreted in terms of a variation of hepatic metabolism of LDL, with direct relevance to the human situation.

The technetium-99m DTPA partition test in the diagnosis of tuberculous meningitis.

Although the blood/cerebrospinal fluid (CSF) bromide concentration ratio is sensitive and specific in the diagnosis of tuberculous meningitis (TBM), bromide-82 is not always available since it is not generally used in nuclear medicine. The use of technetium-99m diethylenetriamine penta-acetic acid (DTPA) for a partition test was compared with that of 82Br in 22 cases. Seven patients were diagnosed as having TBM, 9 patients had viral meningitis and 5 patients had septic meningitis. One normal control subject was also studied. Although the mechanism of transfer of substances across the blood-brain barrier as well as the factors affecting it are still unclear, both 82Br and 99mTc-DTPA cross the blood-brain barrier to a greater extent in TBM than in viral meningitis. Both tracers thus yield decreased serum/CSF concentration ratios in TBM. The accuracy of the 82Br partition test was found to be 90,9% if a critical serum/CSF ratio of 1,3 was chosen, compared with 86,9% for the 99mTc-DTPA partition test if a critical value of 3 was chosen. The use of 99mTc-DTPA offers various advantages, including general availability, lower cost and radiation dose per MBq, as well as the possibility of concomitant brain scintigraphy.

Optimisation of density and contrast yielded by multiformat photographic imagers used for scintigraphy.

The maximum optical density (MOD) and contrast (characterised by an effective gamma, gamma eff) yielded by multiformat photographic imagers used for scintigraphy, was determined by densitometry of a computer image, which consisted of a pattern of uniform squares containing known counts. A series of clinical scintigrams were photographed using various MOD and gamma eff values, and were graded by three experienced clinicians. It was found that a MOD of 1.6 and a gamma eff of 2.9 yielded optimal images for general use if bone scintigrams are also to be photographed. Lesion detectability in phantom images using extreme MOD and gamma eff values that were still clinically acceptable was determined. At very low false-positive rates (less than or equal to 1%) the higher gamma eff yielded a significantly greater lesion detectability (p = 0.02) at an information density of 2200 counts cm-2 in accordance with White-head's theory. It is concluded that quantification and optimisation of density and contrast factors are important and that the technique described enables quality control of multiformat imagers with respect to these factors.

The elimination of errors caused by prior technetium-99m scintigraphy on iodine-131 thyroid uptake measurements.

Coincidence summing of technetium-99m (99mTc) pulses may disturb iodine-131 (131I) thyroid uptake measurements if these are obtained after 99mTc thyroid scintigraphy performed on the same day. The magnitude of the error was assessed in 26 patients. It was found that when pre-dose measurements were subtracted, the 6-hour and 24-hour 131I uptakes could be falsely decreased by up to 137 percentage points using a lower discriminator level of 250 keV and by up to 35 percentage points with a discriminator level of 300 keV. When pre-dose measurements from 99mTc were ignored, there was a general increase in 131I uptake values at 6 hours. Increases of up to 22 and 9 percentage points occurred when 250 keV and 300 keV lower discriminator levels respectively were used. These errors may be eliminated by performing 131I uptake measurements through a 1 mm lead filter.

Quantifying the risks of radiation exposure.

The considerations leading to the recommendation of dose-equivalent limits by the International Commission for Radiological Protection are outlined. The dose-equivalent limits are based on radiation risk factors estimated from effects of radiation observed over many decades. These limits are designed to ensure that radiation exposure does not entail a greater risk than that experienced in other safe occupations or accepted by the general public in everyday life. The risk factors should, however, not be used to assess the risk to patients from diagnostic procedures.

The role of kidney uptake of Tc-99m pertechnetate during quantitation of gastric scintigraphy.

It is shown that during quantitative gastric scintigraphy with Tc-99m pertechnetate significant errors may occur if kidney uptake is ignored. The magnitude of the error was assessed in 12 patients, and could lead to an over-estimation of gastric uptake by up to 20%.

First-pass determination of the right ventricular ejection fraction using two regions of interest and the right anterior oblique view.

The right ventricular ejection fraction (RVEF) was determined on the right anterior oblique view in 9 patients during the first pass of a bolus of technetium-99m employing a gamma camera with high count-rate capability. The RVEF was calculated by using: (i) a fixed end-diastolic region of interest (ROI); and (ii) an end-diastolic and end-systolic ROI. Because of the movement of the tricuspid plane the first of these methods often gave low values, and agreement between the first two peaks was not as good as that when the second method was used. The mean for the second method was in agreement with that in a previous study using a gated first-pass technique and two ROIs but was somewhat higher than those reported by workers using either one ROI or the anterior view.

Temperature distributions obtained with diathermy electrodes implanted into a phantom.

Uniform patterns of heating in a homogeneous phantom were obtained by implanting shortwave diathermy electrodes in a particular configuration. The methods of heating and measurement are described. The technique can be considered for applying localized hyperthermia in the treatment of cancer.

An improved technique for interstitial radiotherapy of the tongue.

An improvement of the plastic tube afterloading technique for interstitial radiotherapy of the tongue is described. This modification allows most of the work to be done outside the patient's mouth. The anchorage for the intra-oral ends of the polythene tubes is produced by transfixing then with a silk thread. This obvioates the need to form loops and simplifies afterloading. It provides a method for crossing the entire lingual end of the implant. All areas and volumes of lower jaw structures are accessible to this form of treatment. Removal of the implant, irrespective of position, is simple and rapid.