Technical note: Sinogram merging to compensate for truncation of projection data in tomotherapy imaging.

An advantage of helical tomotherapy radiation therapy systems is that on-line megavoltage computed tomography (CT) images can be reconstructed to verify patient positioning. One limitation of such systems is that the field-of-view (FOV) of the photon fan-beam is limited by the aperture size of the binary multileaf collimator (MLC) used to modulate treatment beams. For patients larger than the FOV the acquired sinograms will be truncated causing artifacts in the resultant megavoltage CT images. Computer simulations are used to demonstrate that such artifacts can be eliminated or at least reduced by merging appropriately acquired truncated fan-beam sinograms to form a nontruncated parallel-beam sinogram. The necessary fan-beam sinograms are acquired with the patient translated to different offset locations within the gantry. The parallel-beam sinogram is then used to reconstruct the final CT image. The increase in patient dose due to the acquisition of more than one fan-beam sinogram can be reduced by using properly designed binary MLC fields to block redundant projection rays.

Experimental and numerical investigation of the 3D SPECT photon detection kernel for non-uniform attenuating media.

Experimental tests for non-uniform attenuating media are performed to validate theoretical expressions for the photon detection kernel, obtained from a recently proposed analytical theory of photon propagation and detection for SPECT. The theoretical multi-dimensional integral expressions for the photon detection kernel, which are computed numerically, describe the probability that a photon emitted from a given source voxel will trigger detection of a photon at a particular projection pixel. The experiments were performed using a cylindrical water-filled phantom with large cylindrical air-filled inserts to simulate inhomogeneity of the medium. A point-like, a short thin cylindrical and a large cylindrical radiation source of 99Tcm were placed at various positions within the phantom. The values numerically calculated from the theoretical kernel expression are in very good agreement with the experimentally measured data. The significance of Compton-scattered photons in planar image formation is discussed and highlighted by these results. Using both experimental measurements and the calculated values obtained from the theory, the kernel's size is investigated. This is done by determining the square N x N pixel neighbourhood of the gamma camera that must be connected to a particular radiation source voxel to account for a specific fraction of all counts recorded at all camera pixels. It is shown that the kernel's size is primarily dependent upon the source position and the properties of the attenuating medium through Compton scattering events, with 3D depth-dependent collimator resolution playing an important but secondary role, at least for imaging situations involving parallel hole collimation. By considering small point-like sources within a non-uniform elliptical phantom, approximating the human thorax, it is demonstrated that on average a 12 cm x 12 cm area of the camera plane is required to collect 85% of the total count recorded. This is a significantly larger connectivity than the 3 cm x 3 cm area required if scattering contributions are ignored and only the 3D depth-dependent collimator resolution is considered.

Artificial neural networks that use single-photon emission tomography to identify patients with probable Alzheimer's disease.

Single-photon emission tomographic (SPET) images using technetium-99m labelled hexamethyl-propylene amine oxime were obtained from 97 patients diagnosed as having Alzheimer's disease, as well as from a comparison group of 64 normal subjects. Multiple linear regression was used to predict subject type (Alzheimer's vs comparison) using scintillation counts from 14 different brain regions as predictors. These results were disappointing: the regression equation accounted for only 33.5% of the variance between subjects. However, the same data were also used to train parallel distributed processing (PDP) networks of different sizes to classify subjects. In general, the PDP networks accounted for substantially more (up to 95%) of the variance in the data, and in many instances were able to distinguish perfectly between the two subjects. These results suggest two conclusions. First, SPET images do provide sufficient information to distinguish patients with Alzheimer's disease from a normal comparison group. Second, to access this diagnostic information, it appears that one must take advantage of the ability of PDP networks to detect higher-order nonlinear relationships among the predictor variables.

Does gallium uptake in the pulmonary hila predict involvement by non-Hodgkin's lymphoma?

67Ga imaging of non-Hodgkin's lymphoma is useful for evaluating the presence of viable tumour in a residual mass after treatment. However, we have frequently seen gallium uptake in the pulmonary hila without other evidence of lymphoma. To study the significance of this finding, 79 patients with intermediate grade non-Hodgkin's lymphoma were reviewed. Thirty-seven (47%) had abnormal hilar gallium uptake. Twenty-three of these could be fully evaluated, and only five (22%) had hilar lymphoma. A pattern of bilateral, symmetric hilar uptake was seen in 19 patients, but only one had evidence of lymphoma. In 15 cases, this pattern was seen only on single photon emission computed tomography (SPECT). The aetiology of this uptake remains unknown. It is not treatment related, as 12 patients had hilar gallium uptake prior to chemotherapy. Unless confirmed by other methods, hilar gallium uptake should not be attributed to lymphoma, and should not influence patient management.

MAb 170H.82: an evaluation of a novel panadenocarcinoma monoclonal antibody labelled with 99Tcm and with 111In.

A novel method for generating monoclonal antibodies against synthetic tumour-associated glycoconjugates has been developed. One of these monoclonal antibodies, designated 170H.82, was derived against the TF antigen and has been shown in vitro to have a wide range of reactivity with adenocarcinoma. This antibody has been labelled with 111In and 99Tcm and has been evaluated in pilot clinical trials involving 48 patients with a range of adenocarcinoma. Overall clinical accuracy with the radiolabelled antibody was 92%, with the antibody appearing to have particular clinical utility in gynaecological and breast cancers. Single photon emission computed tomographic (SPECT) imaging was shown to improve the quality of the images and to improve the diagnostic sensitivity. We believe that this unique antibody, labelled with 99Tcm, appears to offer promise for routine clinical use in the evaluation of patients with a range of primary and metastatic adenocarcinoma.

Tc-99m HMPAO to demonstrate diffuse cortical necrosis in vivo.

Tc-99m hexamethylpropylene amineoxime (HMPAO) is a novel radiopharmaceutical demonstrated to be a sensitive indicator of abnormalities of cerebral perfusion. Most reports in the literature have evaluated patients with gross perfusion deficits, such as cerebrovascular accidents, and with dementia, where patterns of diffuse perfusion deficit were reported comparable with those seen in PET studies. We report a patient in whom there was the rapid onset of dementia, with the HMPAO images demonstrating diffuse loss of cortical perfusion in a nonfocal, and nonsegmental, fashion. Correlation with postmortem examination demonstrates good concordance between the diffuse nature of HMPAO loss, and diffuse cortical necrosis throughout both cerebral hemispheres. The technique was shown to be more sensitive than transmission CT scanning in demonstrating the extent of the deficit, and it correlated closely with the functional deficits noted in the patient.

Interactive three-dimensional region of interest analysis of HMPAO SPECT brain studies.

An interactive computer program has been developed to align a three-dimensional region of interest (ROI) model to technetium-99m-hexamethylpropylenamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) studies of the brain. The ROI model subdivides the human brain into fourteen discrete regions. A study was performed to determine normal ranges for HMPAO uptake in the ROIs defined by the model, and to assess the relative interobserver variability using the fitting program. HMPAO SPECT studies of twelve normal volunteers were independently analyzed by four observers. Small but significant differences between operators occurred primarily because of difficulty in defining the angle of the orbitomeatal plane on sagittal SPECT images. Despite this difficulty, the program and model have proven useful in defining ranges for normal cerebral perfusion in a healthy adult population. A study of a small group of patients with Alzheimer's dementia suggests that this procedure may be of use in the diagnosis of this disease.

Gallium-67 scintigraphy and non-small-cell bronchogenic carcinoma: a quantitative in-vivo predictive assay?

Gallium-67 scintigraphy has been of limited use in detecting lung cancers and micrometastases. To study its potential for determining the aggressiveness of a cancer, we reviewed the charts of 44 patients with non-small-cell bronchogenic carcinoma who had not been receiving treatment when 67Ga scintigraphy was performed. The mean length of survival for the 18 patients with low or little uptake of the tracer, corrected for tumour size, was 19.7 months, and for the 26 with high uptake 9.4 months (p less than 0.01). Such in-vivo predictive assays may be a rational goal for tumour scintigraphy.

Biological behavior of 67Ga-citrate in New Zealand White rabbits.

The pharmacokinetics, protein binding, excretion and tissue distribution of 67Ga after the administration of 67Ga-citrate to New Zealand White rabbits is described. Data for 67Ga blood levels were best described by an equation with three exponential components exhibiting half lives of 0.25 h, 7.4 h and 19.5 h, with almost all of the activity in a protein bound form. Weekly urinary excretion (approximately 27%), possibly in a metabolized form, and fecal elimination (approximately 20%) were greater than the reported values in man, but there was a similar organ distribution pattern in these animals as in man. The overall biological handling was judged to be similar in both species making the rabbit a suitable model for further 67Ga-citrate studies in vivo.

Effect of the menstrual cycle on gastric emptying.

Gastric emptying of both solid- and liquid-phase markers was assessed in 7 normally-menstruating women who had undergone bilateral Fallopian tube ligations. The women were studied once during the follicular phase of their menstrual cycle and again during the luteal phase. Emptying of the liquid-phase marker was not significantly different during the two phases of the menstrual cycle. However, emptying of the solid-phase marker was significantly slower during the luteal phase of the cycle as compared to the follicular phase. This impairment of gastric emptying of solid was correlated with elevated serum levels of progesterone. This study demonstrates that the rate of gastric emptying of solids may vary with the phases of the menstrual cycle.

Effect of cis-platinum treatment on 67Ga-citrate localization and elimination in rabbits.

The treatment of rabbits with a typical dosage schedule of the chemotherapeutic drug cis-platinum resulted in an increased whole body retention of 67Ga-citrate due to decreased urinary and fecal excretion. The biodistribution of the tracer was also affected with most tissues showing greater accumulation. These changes are primarily related to drug-induced renal dysfunction, but other factors may also be involved.

Gastroesophageal reflux and transit scintigraphy: a comparison with esophageal biopsy in patients with heartburn.

A method for combining scintigraphic studies of esophageal transit and gastroesophageal (GE) reflux is presented. Thirty-two patients with symptoms of GE reflux were studied. The severity of their symptoms was compared to nuclear medicine studies and esophageal mucosal biopsy. Fifteen healthy volunteers were studied as a control group for scintigraphy. The sensitivity of reflux scintigraphy to detect GE reflux as determined by esophageal histology was 70% and its specificity 87%. No relationship was observed between the magnitude of symptoms and the volume of GE reflux. A higher incidence of esophageal transit abnormalities was observed in those patients with histologic features of GE reflux than in those with normal histology. The combination of esophageal reflux and transit scintigraphy provides a way of studying some of the esophageal motor abnormalities associated with GE reflux. For clinical purposes GE reflux scintigraphy seems unsuitable as a single screening test.

Single photon emission tomography of lungs imaged with 99mTc-labeled aerosol.

The use of single photon emission computed tomography (SPECT) and radiolabeled aerosols for lung scanning offers theoretical advantages over conventional gamma camera imaging. We verified the feasibility of using such a system to define particle deposition. First, in two dogs, we detected segments of the lung which had received fewer radiolabeled particles because of obstruction to the airway by a balloon or a lead shot. Second, by comparing axial computed tomography (CT) images to their SPECT counterparts, we were able to demonstrate the effectiveness of SPECT in delineating large thoracic structures such as major vessels and central airways. We feel that SPECT also provides excellent images for qualitative work. We then used SPECT to study aerosol deposition in 13 normal subjects and eight patients. We found that the normal subjects had uniform peripheral deposition, but the eight with abnormal lung function had patchy deposition. Furthermore, we found that regions of abnormal deposition not seen on conventional views could be delineated by tomography. We conclude that this technique will improve our understanding of aerosol deposition in humans by providing a three-dimensional visualization of the lungs and airways.

Effect of doxorubicin on [omega-I-131]heptadecanoic acid myocardial scintigraphy and echocardiography in dogs.

The effects of serial treatment with doxorubicin on dynamic myocardial scintigraphy with [omega-I-131]heptadecanoic acid (I-131 HA), and on global left-ventricular function determined echocardiographically, were studied in a group of nine mongrel dogs. Total extractable myocardial lipid was compared postmortem between a group of control dogs and doxorubicin-treated dogs. A significant and then progressive fall in global LV function was observed at a cumulative doxorubicin dose of 4 mg/kg. A significant increase in the myocardial t1/2 of the I-131 HA was observed only at a higher cumulative dose, 10 mg/kg. No significant alteration in total extractable myocardial lipids was observed between control dogs and those treated with doxorubicin. Our findings suggest that the changes leading to an alteration of myocardial dynamic imaging with I-131 HA are not the initiating factor in doxorubicin cardiotoxicity.

Correction for out-of-focal-plane blurring in a simulated multiplane tomographic scanner.

A technique has been developed to remove out-of-focal-plane blurring from coronal and axial images made using a multiplane tomographic scanner. The technique uses a combined smoothing and differential operator that is applied to the axial images. It has been tested using computer-simulated images, with favorable results. The usefulness of the technique in a real system has yet to be determined.