Observer variation in contouring gross tumor volume in patients with poorly defined non-small-cell lung tumors on CT: the impact of 18FDG-hybrid PET fusion.

PURPOSE: To quantify interobserver variation in gross tumor volume (GTV) localization using CT images for patients with non-small-cell lung carcinoma and poorly defined tumors on CT and to determine whether variability would be reduced if coregistered 2-[18F]fluoro-2-deoxy-d-glucose (FDG)-hybrid positron emission tomography (PET) with CT images were used. METHODS AND MATERIALS: Prospectively, 30 patients with non-small-cell lung carcinoma had CT and FDG-hybrid PET examinations in radiation treatment position on the same day. Images were coregistered using eight fiducial markers. Guidelines were established for contouring GTVs. Three radiation oncologists performed localization independently. The coefficient of variation was used to assess interobserver variability. RESULTS: The size of the GTV defined showed great variation among observers. The mean ratios of largest to smallest GTV were 2.31 and 1.56 for CT only and for CT/FDG coregistered data, respectively. The addition of PET reduced this ratio in 23 of 30 cases and increased it in 7. The mean coefficient of variation for GTV based on the combined modalities was significantly smaller (p < 0.01) than that for CT data only. CONCLUSIONS: High observer variability in CT-based definition of the GTV can occur. A more consistent definition of the GTV can often be obtained if coregistered FDG-hybrid PET images are used.

Spatial and temporal registration of CT and SPECT images: development and validation of a technique for in vivo three-dimensional semiquantitative analysis of bone.

UNLABELLED: The combined use of postoperative 3-dimensional CT and SPECT imaging provides a means of relating anatomy and physiology for the semiquantitative in vivo analysis of bone. This study focuses on the development and validation of a technique that accomplishes this through the registration of SPECT data to a 3-dimensional volume of interest (VOI) interactively defined on CT images. METHODS: Five human cadaver heads served as anthropomorphic models for all experiments. Four cranial defects were created in each specimen with inlay and onlay split-skull bone grafts reconstructed to skull and malar recipient sites. To acquire all images, each specimen was landmarked with 1.6-mm ball bearings and CT scanned. Bone surfaces were coated with 99mTc-doped paint. The locations of the ball bearings were marked with paint doped with 111In. Separate SPECT scans were acquired using the energy windows of 99mTc and 111In. RESULTS: Serial SPECT images aligned with an average root-mean-square (RMS) error of 3.8 mm (i.e., <1 pixel). CT-to-SPECT volume matching aligned with an RMS error of 7.8 mm. Total counts in CT-defined VOIs applied to SPECT data showed a strong linear correlation (r2 = 0.86) with true counts obtained from a dose calibrator. CONCLUSION: The capability of this multimodality registration technique to anatomically localize and quantify radiotracer uptake is sufficiently accurate to warrant further assessment in an in vivo trial.

Outpatient treatment of thyroid cancer using high doses of iodine 131.

OBJECTIVE: To develop a protocol for outpatient high-dose iodine 131 therapy to treat thyroid cancer, to allow therapy to be performed at the patient's convenience and save considerable hospital costs without causing undue radiation exposure to members of the public. METHODS: The radiation safety hazard--both external (from gamma rays emitted from the patient) and internal (from radioactive material in the patient's excretions)--can be calculated according to guides issued by the US Nuclear Regulatory Commission. The protocol aimed to produce an "occupancy factor" of 0.125 or less for the "critical person" (person caring most for the patient) for the entire 72-hour period after administration of 131I. This is the equivalent of 3 hours per day at a distance of 1 m from the patient. RESULTS: Each patient's suitability for outpatient therapy is determined on the basis of the patient's home environment, ability to understand the risks involved and likelihood of compliance, by the referring physician's opinion, through a self-report questionnaire and through a patient interview with the radiation safety officer and the nuclear medicine physician. This protocol has been approved by the Atomic Energy Control Board and has been used to screen 8 patients to date, with 1 patient being denied outpatient treatment. CONCLUSIONS: Outpatient therapies with relatively high doses of 131I can be performed safely. Care must be taken to ensure that the patient's home environment is suitable and that the patient can understand and comply with precautions. If external exposure can be minimized, only basic precautions are needed to ensure that internal contamination does not lead to excessive doses to members of the public.

Brain SPECT imaging and left hemispatial neglect covaried using partial least squares: the Sunnybrook Stroke study.

Hemispatial neglect, characterized as failure to attend to contralesional space, is hypothesized by current neuroanatomical models to result from damage to a network involving the frontal, parietal, and cingulate cortices, basal ganglia, and thalamus. This study investigated this model of neglect in 81 right hemisphere-damaged acute stroke patients using 99mTc-HMPAO single photon emission-computed tomography (SPECT). In order to exploit the inherent collinearity of SPECT regional brain ratios, a novel statistical technique, partial least squares (PLS), was utilized. It makes use of high correlations to identify biologically relevant patterns of brain activity. Averaged ipsilesional cerebellar ratios from 152 brain segments were covaried with performance on subtests of the Sunnybrook Neglect Battery. In this patient sample, the most influential region identified by PLS corresponded to the area surrounding the right temporal-parietal-occipital (TPO) junction that included the right lateral occipital, temporal, and inferior parietal lobes. Hypoperfusion in the medial frontal cortex, including the anterior cingulate, also emerged as significantly associated with more severe neglect. Thus, hypoperfusion in only two of the five hypothesized network regions emerged as significantly associated with hemispatial neglect on SPECT imaging. This work converges with structural imaging studies to suggest that damage to the TPO junction, not just the parietal lobe, may be the critical region for hemispatial neglect. Our study demonstrated the utility of PLS for analyzing functional imaging and behavioral data sets in a clinical population in relation to current neuroanatomical models of neglect.

Brain-behavior correlations in hemispatial neglect using CT and SPECT: the Sunnybrook Stroke Study.

OBJECTIVE: Structural and functional lesion localization in patients with hemispatial neglect. DESIGN: Location and severity of brain damage on CT and SPECT correlated with neglect performance as assessed with a battery of drawings, line bisection, and line and shape cancellation subtests. PATIENTS: Participants included 120 consecutive stroke patients with a single right-hemisphere-damaged lesion on CT who were admitted to the Acute Stroke Care Unit at Sunnybrook Health Science Centre. Of these, 88 also had a SPECT. RESULTS: On CT, 82 patients with neglect (compared with 38 without neglect) had more extensive damage in the parietal and sensorimotor cortex and white matter fiber bundles, including the posterior-superior longitudinal and inferior-frontal fasciculi (p < 0.05). Parietal and anterior cingulate damage best predicted neglect score using the CT data (p < 0.05), and regional blood flow in the parietal cortex best predicted neglect score using the SPECT data (p < 0.05) after controlling for the influence of age and lesion size on multiple linear regression. CONCLUSIONS: Damage in the parietal and anterior cingulate cortex and posterior white matter fiber bundles correlated with hemispatial neglect. Combining structural- and functional-imaging techniques with neurobehavioral analysis can elucidate brain-behavior relationships.

Predictors of hemorrhagic transformation occurring spontaneously and on anticoagulants in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Hemorrhagic transformation (HT) is a common evolution of large-volume ischemic lesions, particularly of cardioembolic origin. We used transcranial Doppler ultrasound (TCD), single-photon emission computed tomography (SPECT) with 99mTc-hexamethylpropyleneamine oxime (HMPAO), and the Toronto Embolic Scale (TES) to decide (1) whether TCD, HMPAO-SPECT, and TES can improve on clinical and CT tests to predict spontaneous HT and (2) whether SPECT can help to predict the outcome of symptomatic HT. METHODS: Prognostic criteria included Canadian Neurological Scale (CNS) scores < or = 50 on admission, early ischemic changes on CT, M1 middle cerebral artery occlusion on TCD, the focal absence of brain perfusion on SPECT, and a high risk of cardiogenic embolism on TES. RESULTS: In part 1, 85 consecutive patients admitted within the first 6 hours were studied. No patient received thrombolysis. HT was found in 11 patients (13%) at 3 to 5 days. Admission CNS and CT were not predictive of HT: odds ratios (95% confidence intervals) were 0.49 (0.18 to 1.23) (P = .1) and 0.88 (0.23 to 3.45) (P = .8), respectively, TCD, SPECT, and TES were significant predictors of HT (P < .05), as follows: TCD, 8.67 (1.42 to 70.59); SPECT, 17.40 (2.69 to 170.89); and TES, 18.13 (2.6 to 406.86). In part 2, 490 consecutive patients were studied and 21 (4%) had symptomatic HT, of which 12 had focal hypoperfusion on SPECT at 4 days after stroke onset and 9 had focal hyperperfusion. Patients with hypoperfusion had larger CT lesions (115 +/- 97 versus 42 +/- 29 cm3; P = .04) and poorer outcome at 2 weeks (CNS, 38 +/- 45 versus 96 +/- 10; P = .001), including death (6/12 versus 0/9; P = .04); compared with those with hyperperfusion on SPECT. CONCLUSIONS: High risk of cardioembolism, M1 middle cerebral artery occlusion, and absence of collateral flow evaluated by TES, TCD, and SPECT help to identify patients at risk for spontaneous HT. Although TES was the most powerful predictor of HT, SPECT is the best single adjunct to the triage of clinical and CT tests. Patients with brain hyperperfusion on HMPAO-SPECT after symptomatic HT have better chances for recovery.

Simple visual analysis of brain perfusion on HMPAO SPECT predicts early outcome in acute stroke.

BACKGROUND AND PURPOSE: Single-photon emission computed tomography (SPECT) is used in patients with acute stroke but as yet is of controversial value. We investigated an association of brain perfusion changes in stroke patients with stroke severity, volume of brain damage, and recovery. METHODS: Consecutive patients with hemispheric stroke were studied prospectively with serial neurological examinations using the Canadian Neurological Scale (CNS), CT. and 99mTc-hexamethylpropyleneamine oxime (HMPAO) SPECT. Visual SPECT patterns of brain perfusion (normal, high, mixed, low, and absent) were correlated with the severity of stroke, lesion volume, and short-term outcome. RESULTS: SPECT studies were performed in a total of 458 consecutive acute stroke patients within 2 weeks after the onset (mean time, 5 days; range, 1 to 12 days). SPECT perfusion patterns correlated with stroke severity (CNS score) during the first 2 weeks (P < .001). Focal absence of brain perfusion on SPECT was associated with the largest volume of brain damage: 104 +/- 84 mL (P < .0001). SPECT perfusion patterns predicted the shortterm outcome: 97% of patients with normal and increased HMPAO uptake made good recovery, 52% of those with decreased perfusion had moderate stroke, and 62% of patients with absent patterns fared badly. In a multiple logistic regression model, admission CNS scores had the strongest predictive value (P = .0001). SPECT had its own prognostic value independent of clinical judgment (P = .03). SPECT statistically improved predictive power of the CNS score (+1% receiver operating characteristic curve area, [X2]2 = 20, P < .001) because of distinction between focal decrease or absence of brain perfusion in patients studied within the first 72 hours of stroke. CONCLUSIONS: Visual brain perfusion patterns correlate with the extent, severity, and short-term outcome of hemispheric stroke. HMPAO SPECT may improve the prognostic value of clinical examination if performed during the first 72 hours of stroke.

Clinical significance of increased uptake of HMPAO on brain SPECT scans in acute stroke.

Single-photon emission computed tomography (SPECT) with 99mtechnetium-hexamethylpropylamineoxime (HMPAO) noninvasively shows brain perfusion in patients after acute stroke. However, the clinical significance of the increased HMPAO uptake remains unclear. In this study, consecutive patients with hemispheric hemorrhagic and ischemic stroke admitted to the hospital were evaluated prospectively. The increased uptake of HMPAO was determined by visual analysis of SPECT images. The pathogenic mechanism of ischemic stroke was determined using the clinical and computed tomography (CT) criteria including the Toronto Embolic Scale. Of the 500 consecutive patients with acute hemispheric stroke, SPECT was performed in 458 at a mean time 5 +/- 7 days after the onset of symptoms. A strong association was found between SPECT perfusion patterns and pathogenic subtypes of stroke (p < 0.0001). Thus, in 95% of patients with intracerebral hemorrhage the focal absence of perfusion was found, and 26% of lacunar infarctions presented with a normal SPECT appearance. The mean volume of lacunar lesions that did not produce significant abnormalities on SPECT was 2.5 +/- 1.2 ml. Increased HMPAO uptake was associated with a cardioembolic mechanism of stroke: High and mixed perfusion patterns were present subacutely in 29% of patients with cardioembolic stroke, compared to 15% of patients with other types of ischemic stroke (p < or = 0.0006). The increased uptake of HMPAO on SPECT as determined by visual analysis is associated with a cardioembolic mechanism of cerebral ischemia, which could be explained by glutathione-mediated trapping of the tracer during reperfusion and later in newly developed granulation tissue. HMPAO-SPECT may help in early management decisions since it indicates stroke pathogenesis and evolution.

Effects of non-linear flow and spatial orientation on technetium-99m hexamethylpropylene amine oxime single-photon emission tomography.

The effects of two post-acquisition corrections on the visual and quantitative analysis of technetium-99m hexamethylpropylene amine oxime (HMPAO) single-photon emission tomography (SPET) were determined. The corrections were for: (1) the improper spatial orientation of the patient data sets, and (2) the non-linear uptake of HMPAO across the blood-brain barrier. Reorienting the SPET image data sets removed observers' uncertainty in assessment caused by suspected head tilt; however, it increased their uncertainty due to perceived subtle perfusion deficits. Applying the correction to compensate for the decrease in uptake of HMPAO in high-flow regions resulted in an increase in the number of positive assessments. In a study involving 30 patient studies, intra-observer reliability increased from 62% to 83% (average of two observers) after applying both of the corrections, while inter-observer reliability improved from 62% to 81%. Quantitative methods of analysing the images are also affected by the corrections. In an ROI-based classification scheme, the quantitative assessments of more than one-half of the images are affected by the two corrections. These results need to be considered when comparing both quantitative and visual results from different studies in which the corrections may or may not have been applied.

Noninvasive assessment of intracranial perfusion in acute cerebral ischemia.

Single-photon emission computed tomography (SPECT) and transcranial Doppler sonography (TCD) may help to determine a target group of patients with maximum therapeutic response for tissue rescue after acute stroke. As previously described, the cerebral perfusion index represents a combination of these techniques, and is calculated by multiplying assigned values for TCD and SPECT perfusion patterns. The three grades of cerebral perfusion index (1-5, 6-12, 15-20) may predict short-term outcome if the index is based on SPECT and TCD performed within the first 6 hours after stroke. A total of 30 consecutive patients were studied (18 with middle cerebral artery stroke and 12 with transient ischemic attack or minor stroke). Neurological deficit was scored using the Canadian Neurological Scale. SPECT and TCD were performed 4 +/- 2 hours after the onset. Forty-five minutes were required to perform both tests, evaluate the results, and calculate the cerebral perfusion index. The mean score (+/- standard deviation) of the neurological deficit on admission was 84 +/- 20 in patients with transient ischemic attack/minor stroke and 54 +/- 33 in patients with stroke (p < 0.009). The volume of ischemic lesion was measured on computed tomography scans performed more than 3 days after the ictus. Patients with transient ischemic attack/minor stroke had lesion volumes of 8 +/- 7 cm3 compared to 72 +/- 26 cm3 for those with stroke (p < 0.0001). The mean cerebral perfusion index in the transient ischemic attack group was 18 +/- 4, while in the stroke group it was 4 +/- 1 (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of thresholds for detection of cerebellar blood flow deficits in brain SPECT images.

UNLABELLED: Two observer studies were performed to determine the threshold (i.e., ratio of the counts in a lesion area to the counts in the corresponding contralateral region) at which two experienced observers diagnosed blood flow deficits in the cerebellum in 99mTc-HMPAO SPECT scans to be clinically significant, and investigate the effect of the intensity mapping scale on the detectability of lesions. METHODS: Lesions representing blood flow deficits varying from no decrease to a 12.5% decrease were simulated in 300 patient images. The first study, a receiver-operator characteristics (ROC) experiment, used two observers to compare the detectability of lesions with three intensity mapping scales: two pseudocolor scales, and a linear gray scale. A second "threshold-criterion" study was done to estimate the threshold at which observers determine deficits to be clinically significant. RESULTS: In the ROC study, the observers were more accurate in detecting lesions displayed in pseudocolor than in gray scale. In the threshold-criterion study, the threshold at which observers assessed clinically significant deficits was found to range between 0.900 and 0.950 (corresponding to a 5%-10% decrease in counts), depending on the observer, and the intensity mapping scale. For both observers, the detection threshold was higher (i.e., closer to 1.0) with the pseudocolor scale than with the gray scale. CONCLUSION: The definition of a threshold value for use in quantitative techniques is dependent on both the observer and the intensity mapping scale. Observers were more accurate with the pseudocolor scales.

Cerebral perfusion index: a new marker for clinical outcome in acute stroke.

Single-photon emission computed tomography (SPECT) and transcranial Doppler (TCD) ultrasound are of good prognostic value in acute stroke, and combined they may be an accurate way to determine a target group of patients with maximum therapeutic response. Seventy consecutive patients were studied (42 with middle cerebral artery strokes, 18 with transient ischemic attacks {TIAs}; 10 were excluded due to failure of insonation). Two SPECT studies were performed at 2.1 +/- 1.2 and 13.8 +/- 3.1 days after onset. Serial TCD studies were done at 10 hours and at the time of the SPECT studies. Neurological deficit was scored on admission and 2 weeks later (using the Canadian Neurological Scale). Cerebral perfusion index (CPI) was derived by multiplying the values for TCD and SPECT patterns. Positive correlation was obtained in all 16 patients in whom cerebral angiography was performed within the first 3 days after onset. The occlusive TCD pattern and absence of perfusion on SPECT were common in the stroke group (19/42 patients) and were never seen in those with TIAs. A normal TCD pattern and normal perfusion on SPECT were more common in the patients with TIAs (9/18 vs 8/42, p = 0.02; 5/10 vs 1/40, p = 0.0003). The occlusive TCD and SPECT patterns were associated with the highest mean infarction volume (147 +/- 87 vs 19 +/- 21, p less than 0.0001) and all nonocclusive TCD and SPECT patterns were associated with the better short-term outcome (43.2 +/- 33.9 vs 92.4 +/- 20.2, p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of myocardial contusion following blunt chest trauma.

A prospective study was undertaken at a regional trauma unit (RTU) to determine the significance of cardiac complications in patients with blunt chest trauma. Radionuclide angiographic (RNA) imaging was performed as soon as possible after admission and Holter monitors were applied for 72 hours. Routine investigations included serial cardiac enzyme measurements and 12-lead electrocardiograms. Dysrhythmias were classified and ventricular dysrhythmias were stratified by ventricular ectopic score (VES) as ventricular tachycardia (4) or greater than 100 premature ventricular contractions (PVCs)/hour (3). Three hundred twelve patients were entered into the study. Analysis of dysrhythmias revealed 18 patients with a VES of 4 and nine patients with a VES of 3; there were no serious consequences. The most significant dysrhythmia as a marker of outcome was atrial fibrillation (n = 9); five of these patients died, but all of associated noncardiac injuries. A review of abnormal RNAs revealed that all associated mortalities were attributed to noncardiac injuries. A review of postmortem reports and hospital records revealed that no deaths were attributed to cardiac failure or dysrhythmia. Thus the incidence of clinically significant dysrhythmias or other cardiac complications resulting from blunt trauma to the heart may be overestimated.

Indium-111 chloride scintigraphy in adult osteomyelitis.

Osteomyelitis is a common clinical problem that may be difficult to diagnose. We compared the performance of indium-111-labeled white cells ([111In]WBC) to 111In chloride ([111In]Cl) in two groups of adult patients suspected to have osteomyelitis or septic arthritis. Using [111In] WBC, 52 scans were performed on 51 patients. Nineteen patients had osteomyelitis. The sensitivity was 84% and specificity 82%. Using [111In]Cl, 48 scans were performed on 47 patients. Twelve had osteomyelitis. Sensitivity was 91%, and specificity was 89%. In each group, one false-negative study occurred in vertebral osteomyelitis. Three false-negative studies using [111In]WBC were due to failure to distinguish between combined bone and soft-tissue infection and soft-tissue infection alone. False-positive studies in both groups were due to overlying soft-tissue infection or inflammatory arthritis. Chi-squared test showed no significant difference in performance between the two agents. Indium-111 chloride is easier to prepare and use than [111In]WBC, which requires a time-consuming labeling process.