Distinguishing tumor recurrence from irradiation sequelae with positron emission tomography in patients treated for larynx cancer.

PURPOSE: Distinguishing persistent or recurrent tumor from postradiation edema, or soft tissue/cartilage necrosis in patients treated for carcinoma of the larynx can be difficult. Because recurrent tumor is often submucosal, multiple deep biopsies may be necessary before a diagnosis can be established. Positron emission tomography with 18F-2fluoro-2deoxyglucose (FDG) was studied for its ability to aid in this problem. METHODS AND MATERIALS: Positron emission tomography (18FDG) scans were performed on 11 patients who were suspected of having persistent or recurrent tumor after radiation treatment for carcinoma of the larynx. Patients underwent thorough history and physical examinations, scans with computerized tomography, and pathologic evaluation when indicated. Standard uptake values were used to quantitate the FDG uptake in the larynx. RESULTS: The time between completion of radiation treatment and positron emission tomography examination ranged from 2 to 26 months with a median of 6 months. Ten patients underwent computed tomography (CT) of the larynx, which revealed edema of the larynx (six patients), glottic mass (four patients), and cervical nodes (one patient). Positron emission tomography scans revealed increased FDG uptake in the larynx in five patients and laryngectomy confirmed the presence of carcinoma in these patients. Five patients had positron emission tomography results consistent with normal tissue changes in the larynx, and one patient had increased FDG uptake in neck nodes. This patient underwent laryngectomy, and no cancer was found in the primary site, but nodes were pathologically positive. One patient had slightly elevated FDG uptake and negative biopsy results. The remaining patients have been followed for 11 to 14 months since their positron emission studies and their examinations have remained stable. In patients without tumor, average standard uptake values of the larynx ranged from 2.4 to 4.7, and in patients with tumor, the range was 4.9 to 10.7. CONCLUSION: Positron emission tomography with labeled FDG appears to be useful in distinguishing benign from malignant changes in the larynx after radiation treatment. This noninvasive technique may be preferable to biopsy, which could traumatize radiation-damaged tissues and precipitate necrosis.

Sensitivity, resolution and image quality with a multi-head SPECT camera.

This investigation sought to determine which collimation factors were most important in providing superior image quality with a three-headed SPECT device. The relationship between sensitivity, resolution and SPECT image quality was studied. Two different sets of parallel-hole collimators were used. The ultrahigh-resolution collimators have higher spatial resolution (8.9 versus 11.0 mm), but only 55% of the sensitivity of the high-resolution collimators. A phantom with hot rods was imaged with both collimator sets. Observers compared images with the ultrahigh-resolution collimators to images of varying counts with the high-resolution collimators and determined which high-resolution images matched the ultrahigh-resolution images in image quality. Eleven patient studies were acquired with both collimator sets for equal time, and observers chose which image set they preferred. Transverse images of brain and liver studies were simulated with varying resolution and counts and subjectively compared. The phantom study indicated that the improvement in resolution led to image quality comparable to increasing the number of counts by a factor of 2.5 to 3.4. The clinical studies showed that the ultrahigh-resolution collimators were preferred in a large majority of the cases. These trends were also seen in the simulation study. These results confirm that higher resolution collimators should be used with multihead SPECT devices. The improvement in resolution more than compensates for the loss in sensitivity, leading to an overall improvement in image quality.

Field-flood requirements for emission computed tomography with an Anger camera.

Emission computed tomography with a rotating camera places stringent requirements on camera uniformity and the stability of camera response. In terms of clinical tomographic imaging, we have studied the statistical accuracy required for camera flood correction, the requirements for flood accuracy, the utility and validity of flood and data image smoothing to reduce random noise effects, and the magnitude and effect of camera variations as a function of angular position, energy window, and tuning. Uniformity of the corrected flood response must be held to better than 1% to eliminate image artifacts that are apparent in a million-count image of a liver slice. This requires calibration with an accurate, well-mixed flood source. Both random fluctuations and variations in camera response with rotation must be kept below 1%. To meet the statistical limit, one requires at least 30 million counts for the flood-correction image. Smoothing the flood image alone introduces unacceptable image artifacts. Smoothing both the flood image and data, however, appears to be a good approach toward reducing noise effects. Careful camera tuning and magnetic shield design provide camera stability suitable for present clinical applications.

Performance evaluation of SPRINT, a single photon ring tomography for brain imaging.

SPRINT, a prototype single photon tomograph, has been designed primarily for high-resolution brain imaging in humans with I-123-labeled compounds such as iodoamphetamine, hydroxyiodopropyldiamine (HIPDM), and iodobenzene (IBZ). SPRINT uses a ring of stationary, discrete Nal detectors, and fan-beam sampling is accomplished with a rotating eight-slit aperture ring that acquires a complete projection set in 1/8 revolution. In-plane and cross-plane resolutions are 8mm and 10mm FWHM, respectively, measured on axis. Sensitivity with an 18% energy window is 1000 cprs per microCi/cc for Tc-99m in a 20 cm diameter phantom. A detailed evaluation of system performance has been completed, and preliminary human brain blood flow images have been obtained using HIPDM.

Intermodality, retrospective image registration in the thorax.

UNLABELLED: The purpose of this study was to develop an accurate, retrospectively applicable procedure for registering thoracic studies from different modalities in a short amount of time and with minimal operator intervention. METHODS: CT and PET studies were acquired from six patients. The pleural surfaces in both image sets were determined by segmenting based on 50% of the maximum soft-tissue value in the study. These surfaces were converted into three-dimensional volumes and used to register the CT and PET studies in three dimensions using a sum of least squares fitting approach. The registered PET study was then displayed in a hot metal scale overlayed on top of the gray scale CT study. The accuracy of the fit was evaluated through a phantom study and preliminary clinical evaluation. RESULTS: A phantom study was performed to determine the limits of this technique. The accuracy was determined to be less than 2.3 mm in the x and y direction and 3 mm in the z direction. Preliminary clinical evaluation was also performed with encouraging results. CONCLUSION: This technique accurately registers PET and CT images of the thorax, retrospectively, without the need for external fiducial markers or other a priori action.

Evaluation of emission-transmission registration in thoracic PET.

UNLABELLED: The intent of this investigation was to quantitate the amount of misregistration between PET emission and transmission scans of the thorax that occurs in a normal clinical environment. METHODS: The data from 17 FDG myocardial studies were evaluated. Prior to injection, a transmission study was acquired for 15 min using a 68Ge/68Ga ring source. The location of the cross-hairs from a laser alignment system was marked on the patient who was then removed from the scanner and injected with 10 mCi of FDG. After 45 min, the patient was placed back on the table and repositioned with the previously placed marks and a 15-min emission scan was acquired. The outline of the lungs on both the transmission and emission images was manually segmented. Both attenuation-corrected and noncorrected emission images were evaluated and the one that provided clearer visualization of the outline of the lungs was chosen for segmentation. The segmented contours of the transmission and emission scans were then registered with the method described by Pelizzari et al. using the transmission image as the "head" and the emission image as the "hat." The allowable transformations were x and y shifts and rotation in the transverse plane. RESULTS: Shifts in the x-axis averaged 2.4 mm (range: 0.2-7.3 mm, 80% less than 3.3 mm) with shifts in the y-axis averaging 2.6 mm (range: 0.1-8.7 mm, 80% less than 2.4 mm) and rotations in the transverse plane averaging 1.6 degrees (range: 0.2 to 5.1 degrees, 80% less than 2.4 degrees). A phantom study indicated that the accuracy of this method of evaluating misregistration was 2.35 mm and 1.81 mm in the x and y directions, respectively. CONCLUSION: Our preliminary evaluation indicates that careful application of laser alignment is an adequate method of registration in most cases.

Emission tuned-aperture computed tomography: a novel approach to scintimammography.

UNLABELLED: Emission tuned-aperture computed tomography (ETACT) is a new approach to acquiring and processing scintimammography data. A gamma camera with a pinhole collimator is used to acquire projections of the radionuclide distribution within the breast. Fiducial markers are used to reconstruct these projections into tomographic slices. Simulation and phantom experiments were performed to evaluate the potential of the ETACT method. METHODS: In the simulation study, a hemispheric object of 15 cm in diameter was constructed to model a breast. A ray-tracing technique was used to generate ideal projections. These were blurred and noise was added to create images that resemble scintigraphic images. Tumor size, pinhole size, and target-to-nontarget radioactivity ratios (TNTs) were varied. The simulated projections were reconstructed into slices, and contrast and contrast-to-noise ratios were calculated to evaluate the effect of pinhole size. These results were compared with a simulated planar acquisition of the same object. A preliminary phantom evaluation was performed using an 8-mm "tumor" with a 10:1 TNT to validate the simulation results. RESULTS: A 3-mm pinhole was shown by the simulation study to be the optimal size. The ETACT images consistently yielded higher contrast than simulated planar images. The phantom study validated the simulation results and showed the feasibility of ETACT in a simulated clinical environment. CONCLUSION: ETACT is shown to be useful for imaging tumors <1 cm in diameter. Because ETACT requires only a gamma camera with a pinhole collimator, it has the potential to be applied in any hospital in a simple, flexible, and practical manner.

The usefulness of positron emission tomography in evaluating patients for pulmonary malignancies.

STUDY OBJECTIVE: Positron emission tomography (PET) can contribute to diagnosing and staging lung cancer, but it has not been determined whether this information influences patient care. DESIGN: We reviewed the effects of thoracic PET scan results during an 11-month period. For each patient, physicians ordering these scans reported how PET specifically altered management, and graded the ease of interpretation and overall usefulness of PET on a 5-point scale. In addition, to appraise general attitudes about PET, we surveyed 488 national American Thoracic Society (ATS) members and 44 physicians at our comprehensive cancer center. RESULTS: One hundred twenty-six questionnaires regarding patients were mailed to 37 ordering physicians, and 98 responses (78%) were returned, primarily by cardiothoracic surgeons (35%) and pulmonologists (47%). Respondents reported that PET provided new information in 83 patients (85%) and altered patient management in 64 cases (65%). Major effects on management included decisions regarding biopsy (n = 16), surgery (n = 16), and palliative treatment (n = 16). Chest clinicians found PET to be more helpful (4.4 vs 3.9, p = 0.007) and easier to interpret (4.2 vs 3.7, p = 0.025) than other specialists. Among 139 ATS members (28%) responding to the general survey, 51 members (39%) had access to PET. PET was more frequently available to university-based (49%) than community-based (27%) physicians (p = 0.016). The majority of physicians without current access to PET (69%) indicated that they would like to have it available. ATS members with access to PET reported that PET results generally affect decisions regarding biopsy or surgery most often, but found the procedure less helpful than physicians at our center (2.77 vs 3. 56, p = 0.003) and ordered it less often for lung cancer staging (60% vs 96%, p = 0.002). CONCLUSION: PET scanning is useful in the management of patients with suspected thoracic malignancies, but impressions about its roles vary, with PET regarded more highly where, as at our center, it is used more often. Whether PET alters patient outcomes requires investigation.

Characterization of the rotating display.

The rotating display is a useful method for reviewing single photon emission computed tomography (SPECT) data. This study evaluated the requirements for a subjectively pleasing and useful implementation of this technique. Twelve SPECT data sets were modified and viewed by several observers who recorded the minimum framing rates for apparent smooth rotation, 3D effect, effects of image size, and other parameters. The results showed that a minimum of 16 frames was needed for a useful display. Smaller image sizes and more frames were preferred. The recommended minimal framing rate for a 64-frame study is 16-17 frames per second and for a 32-frame study, 12-13 frames per second. Other enhancements also were useful.

Liver-spleen studies with the rotating gamma camera. I: Utility of the rotating display.

The clinical utility of a computer-generated dynamic cine display (rotating display) of the unprocessed projection images of the liver and spleen obtained with rotating gamma-camera tomography was prospectively compared with that of the standard multi-view static scintigram display. Two hundred cases were independently and blindly analyzed by three observers. Each study was coded from 1-5, indicating the certainty of normality or abnormality present. When abnormality was noted, the study was assessed for the presence of metastatic disease, inhomogeneous uptake, hepatosplenomegaly, and colloid distribution shift. ROC analysis was then performed on the initial coding for certainty of abnormality, and the causes for discrepancies were evaluated from the assessment of the type of abnormality present. No significant interdisplay differences could be demonstrated. In the small percentage of cases where interdisplay disagreement occurred, this was usually accompanied by marked interobserver variation and was most commonly due to differing assessment of organ size. It is concluded that the static and rotating display formats can be used interchangeably in the evaluation of technetium-99m-labeled sulfur colloid liver studies.

Liver-spleen studies with the rotating gamma camera. II: Utility of tomography.

A prospective comparison of conventional scintigrams and single-photon emission computed tomography (SPECT) studies of the liver and spleen was carried out. Care was taken to insure high-quality, artifact-free studies. Two hundred patients were imaged by both methods. A definitive diagnosis of normal was established in 86 cases, abnormal in 107 cases, and seven cases were indeterminate. All studies were read by two observers and graded as to degree and type of abnormality seen. ROC curves were constructed and errors of interpretation studied to identify problems. One observer showed no difference in performance between the two methods. The other showed a small improvement with SPECT. Image artifacts apparently contributed to errors of interpretation in 24 of 54 cases using SPECT. SPECT appears comparable with conventional scintigraphy and may improve specificity. Improvements are needed in SPECT imaging equipment and image display capability to realize fully the potential of SPECT.

Salivary gland tumors: pretherapy evaluation with PET.

PURPOSE: To determine whether positron emission tomography (PET) can help differentiate benign from malignant lesions of the salivary glands before surgery. MATERIALS AND METHODS: Masses of the salivary glands were examined in 26 patients by means of computed tomography, magnetic resonance imaging, PET, biopsy (n = 18), and surgery. Contiguous PET scans were obtained from the midcranium to the lower chest 45 minutes after administration of 370 MBq (10 mCi) of fluorine-18 fluorodeoxyglucose (FDG). Standard uptake values (SUVs) were determined for all suspect lesions and for normal parotid glands and cerebellum. RESULTS: All lesions were visualized, and all but two showed some increase in FDG uptake. PET findings helped correctly differentiate benign from malignant masses in 18 (69%) but were false-positive for malignancy in eight (31%). SUV analysis, lesion-to-normal SUV ratios, and lesion-to-cerebellar SUV ratios also failed to differentiate the lesions. CONCLUSION: FDG PET is not useful in classifying salivary gland tumors as benign or malignant.

Evaluation of brain activity in FDG PET studies.

PURPOSE: A tool (Gemini) was developed for quantifying regions of interest (ROIs) in registered MR and PET data. Its use was validated through phantom and simulated studies. METHOD: Hot spheres were imaged in a phantom (3:1 and 5:1 target-to-nontarget ratios). The computerized 3D Hoffman brain phantom was used to simulate PET studies. Spherical local activity features of two diameters (4 and 10 mm) and five intensities (5, 15, 25, 50, and 100% increase over gray matter) were added to the data in the thalamus and Brodmann area 37. The data were reprojected into sinograms and blurred with a 7 mm kernel. Poisson noise was added, and the sinograms were then reconstructed and analyzed using both SPM96 and Gemini spherical ROIs. RESULTS: Based on phantom and simulated data, the 95th percentile of intensity within a Gemini ROI afforded a reasonable joint optimization of variance (reliability) and accuracy (validity). SPM96 and Gemini results were similar for the larger (10 mm) feature, but in this application, Gemini was more sensitive than SPM96 for the small feature (4 mm). CONCLUSION: Gemini, a tool for display and measurement of spherical ROIs in registered PET and MR data, is precise and accurate for testing hypotheses of differences in localized brain activity, comparing favorably with SPM96.

Serial positron emission tomography scans following radiation therapy of patients with head and neck cancer.

BACKGROUND: A single institution study was undertaken to evaluate the role of positron emission tomography (PET) scans with fluorodeoxyglucose (FDG) prior to radiation and following radiation. METHODS: Forty-five patients with head and neck cancers were evaluated with FDG-PET scans as well as either CT or MRI prior to treatment with definitive radiation (RT). These same scans were obtained following completion of RT at 1 month (36 patients), 4 months (28 patients), 12 months (19 patients), and 24 months (15 patients). Standard uptake values (SUV) normalized for blood glucose and lean body mass were calculated on the initial and 1-month post-treatment PET scans. RESULTS: Fifteen patients are alive without evidence of disease at 24 to 52 months following RT. Initial SUVs were calculated on the primary tumor site and ranged from 2.5 to 28.5. These values did not have any correlation with local control when examined for the entire group, primary site, or T stage. One-month post-RT SUV ranged from 1.8 to 6.24. Of the 36 1-month post-RT PET scans, six were interpreted as positive for residual disease and were confirmed by biopsy. Four of the five scans, which were interpreted as equivocal, were positive on biopsy. Seven of the 25 scans, which were interpreted as negative for tumor, were positive on biopsy. Four-month scans were more accurate for disease with disease noted in 0 of 18 negative scans, 6 of 7 positive scans, and 2 of 3 equivocal scans. CONCLUSIONS: PET is useful for initial imaging of head and neck cancers. SUV does not appear to be useful for predicting outcome following treatment with RT. One-month post-RT scans were inaccurate for predicting the presence of cancer. Four-month post-RT scans were a better predictor for the presence of cancer.

Diagnosis of intracranial lymphoma in patients with AIDS: value of 201TI single-photon emission computed tomography.

OBJECTIVE: Although the prevalence of intracranial lymphoma is high among patients with AIDS, current imaging techniques are not reliable for differentiating this tumor from other common nonneoplastic lesions, such as those seen in toxoplasmosis. The purpose of this study was to prospectively investigate the use of 201Tl single-photon emission computed tomography (SPECT) in identifying intracranial lymphoma in patients with AIDS. SUBJECTS AND METHODS: Thirteen patients with AIDS and intracranial masses underwent 201Tl imaging with a three-headed SPECT camera. Sic of the 13 were subsequently proved to have lymphoma. Studies were interpreted prospectively as showing tumor if uptake of 201Tl was increased in the region where the lesion was seen on MR images. A lesion-to-nonlesion uptake ratio (counts/pixel) was calculated retrospectively. RESULTS: The SPECT images of six patients were interpreted prospectively as showing no lymphoma. Uptake ratios in these six patients were 0.77-1.95 (mean, 1.45). In each, tumor was excluded as a final diagnosis (four had toxoplasmosis, one had progressive multifocal leukoencephalopathy, and one had venous angioma). Among the seven patients with SPECT images interpreted as showing lymphoma, six were later proved to have lymphoma (uptake ratio: mean, 3.65; range, 2.95-4.30; p < .005). The SPECT findings in the seventh patient were classified as false-positive for tumor on the basis of the prospective interpretation of the images; three concurrent infections were found at autopsy. The uptake ratio in this patient was low (1.81), suggesting that quantification might have diagnostic usefulness for improving accuracy. CONCLUSION: This preliminary study indicates that 201Tl SPECT might be a useful, noninvasive method for differentiating intracranial lymphoma from nonneoplastic lesions in patients with AIDS.

Reduced regional and global cerebral blood flow during fenoldopam-induced hypotension in volunteers.

UNLABELLED: Dopamine has a wide spectrum of receptor and pharmacologic actions that may affect cerebral blood flow (CBF). A new, selective dopamine-1 agonist, fenoldopam, is a potent systemic vasodilator with moderate alpha(2)-receptor affinity. However, the effects of fenoldopam on the cerebral circulation are undefined. We therefore hypothesized that infusion of fenoldopam would decrease mean arterial blood pressure (MAP) and might concurrently decrease CBF via vascular alpha(2)-adrenoreceptor activation in awake volunteers. We studied nine healthy normotensive subjects, using positron emission tomography to measure CBF in multiple cortical and subcortical regions of interest. In addition, bioimpedance cardiac output and middle cerebral artery blood flow velocity were determined during fenoldopam-induced hypotension. Three men and four women, aged 25-43 yr, completed the study. Fenoldopam infused at 1.3 +/- 0.4 microg. kg(-1). min(-1) (mean +/- SD) reduced MAP 16% from baseline: from 94 (89-100) mm Hg (mean [95% confidence interval]) to 79 [74-85] mm Hg (P < 0.0001). During the fenoldopam infusion, both cardiac output (+39%), and heart rate (+45%) increased significantly, whereas global CBF decreased from baseline, 45.6 [35.6-58.5] mL. 100 g(-1). min(-1), to 37.7 [33.9-42.0] mL. 100 g(-1). min(-1) (P < 0.0001). Despite restoration of baseline MAP with a concurrent infusion of phenylephrine, global CBF remained decreased relative to baseline values at 37.9 [34.0-42.3] mL. 100 gm(-1). min(-1) (P < 0.0001). Changes in middle cerebral artery velocity did not correlate with positron emission tomography-measured changes of CBF induced by fenoldopam, with or without concurrent phenylephrine. IMPLICATIONS: In awake volunteers with (presumably) intact cerebral autoregulation,fenoldopam-induced hypotension significantly decreased global cerebral bloodflow (CBF). Clinicians should be aware of these pharmacodynamic effects when choosing a vasodilator to control blood pressure, especially in situations where control of CBF, cerebral blood volume, and intracranial pressure are therapeutic priorities.