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1.  Computer-assisted lateralization of unilateral temporal lobe epilepsy using Z-score parametric F-18 FDG PET images 
Background
To evaluate the use of unbiased computer-assisted lateralization of temporal lobe epilepsy (TLE) by z-score parametric PET imaging (ZPET).
Methods
38 patients with histologically proven unilateral TLE due to pure hippocampal sclerosis, referred for pre-surgical PET evaluation of intractable seizure over a 5-year period, were included. The F-18 FDG images were oriented along temporal long axis and then transformed into ZPET images on a voxel by voxel basis. Multiple regions of interests (21 in total) were placed on cortical, subcortical and cerebellar structures on twenty-eight out of 38 patients with totally seizure-free (class I) outcome. Paired t-tests with Bonferroni correction were used to determine the location of the most asymmetric regions as variables for subsequent discriminant analysis of the entire group of the patients.
Results
The computer program identified the anterior half of the temporal lobe (p < 0.0005) and thalami (p = 0.021) as the most asymmetric regions in TLE patients with Class I outcome. Discriminant analysis using z-scores from a total of 8 ROIs (in 4 pairs) on these structures correctly lateralized thirty-seven out of 38 (97%) patients (sensitivity = 94%; specificity = 100%). The only false localization came from a patient with equivocal z-scores on the temporal lobes and this patient turned out to have poor outcome.
Conclusion
The computer-assisted lateralization of TLE using ZPET provides an accurate, fast and objective way of seizure evaluation.
doi:10.1186/1471-2385-7-5
PMCID: PMC2194666  PMID: 17980040
2.  Comparison of 2D, 3D high dose and 3D low dose gated myocardial 82Rb PET imaging 
Background
We compared 2D, 3D high dose (HD) and 3D low dose (LD) gated myocardial Rb-82 PET imaging in 16 normal human studies. The main goal in the paper is to evaluate whether the images obtained by a 3D LD studies are still of comparable clinical quality to the images obtained with the 2D HD or 3D HD studies.
Methods
All 2D and 3D HD studies were performed with 2220 MBq of Rb-82. The 3D LD were performed with 740 MBq of Rb-82. A GE Advance PET system was used for acquisition. Polar maps were created and used to calculate noise among (NAS) and within (NWS) the segments in the noise analysis. In addition, the contrast between left ventricular (LV) wall and LV cavity was also analysed. For 13 subjects, ejection fraction (EF) on 2D and 3D studies was calculated using QGS program.
Results
For the H20 reconstruction filter, the mean contrast in mid-ventricular short-axis slice was 0.33 ± 0.06 for 2D studies. The same contrast for the 3D HD studies was 0.38 ± 0.07 and for 3D LD, it was 0.34 ± 0.08. For the 6 volunteers where 3D HD was used, NAS was 3.64*10-4 and NWS was 1.79*10-2 for 2D studies, and NAS was 3.70*10-4 and NWS was 1.85*10-2 for 3D HD studies, respectively. For the other 10 volunteers where 3D LD was used, NAS was 3.85*10-4 and NWS was 1.82*10-2 for the 2D studies, and NAS was 5.58*10-4 and NWS was 1.91*10-2 for the 3D LD studies, respectively. For the sharper H13 filter, the data followed the same pattern, with slightly higher values of contrast and noise. EF values in 2D and 3D were close. The Pearson's correlation coefficient was 0.90. The average difference from 13 subjects was 8.3%.
Conclusion
2D and 3D HD gating Rb-82 PET cardiac studies have similar contrast, ejection fractions and noise levels. 3D LD gating imaging, gave comparable results in terms of contrast, EF and noise to either 2D or 3D HD gating PET imaging. 3D LD PET gated imaging can make Rb-82 PET cardiac imaging more affordable with significantly less radiation exposure to the patients.
doi:10.1186/1471-2385-7-4
PMCID: PMC2140263  PMID: 17953754
3.  Toxicology evaluation of radiotracer doses of 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT) for human PET imaging: Laboratory analysis of serial blood samples and comparison to previously investigated therapeutic FLT doses 
Background
18F-FLT is a novel PET radiotracer which has demonstrated a strong potential utility for imaging cellular proliferation in human tumors in vivo. To facilitate future regulatory approval of 18F-FLT for clinical use, we wished to demonstrate the safety of radiotracer doses of 18F-FLT administered to human subjects, by: 1) performing an evaluation of the toxicity of 18F-FLT administered in radiotracer amounts for PET imaging, 2) comparing a radiotracer dose of FLT to clinical trial doses of FLT.
Methods
Twenty patients gave consent to a 18F-FLT injection, subsequent PET imaging, and blood draws. For each patient, blood samples were collected at multiple times before and after 18F-FLT PET. These samples were assayed for a comprehensive metabolic panel, total bilirubin, complete blood and platelet counts. 18F-FLT doses of 2.59 MBq/Kg with a maximal dose of 185 MBq (5 mCi) were used. Blood time-activity curves were generated for each patient from dynamic PET data, providing a measure of the area under the FLT concentration curve for 12 hours (AUC12).
Results
No side effects were reported. Only albumin, red blood cell count, hematocrit and hemoglobin showed a statistically significant decrease over time. These changes are attributed to IV hydration during PET imaging and to subsequent blood loss at surgery. The AUC12 values estimated from imaging data are not significantly different from those found from serial measures of FLT blood concentrations (p = 0.66). The blood samples-derived AUC12 values range from 0.232 ng*h/mL to 1.339 ng*h/mL with a mean of 0.802 ± 0.303 ng*h/mL. This corresponds to 0.46% to 2.68% of the lowest and least toxic clinical trial AUC12 of 50 ng*h/mL reported by Flexner et al (1994). This single injection also corresponds to a nearly 3,000-fold lower cumulative dose than in Flexner's twice daily trial.
Conclusion
This study shows no evidence of toxicity or complications attributable to 18F-FLT injected intravenously.
doi:10.1186/1471-2385-7-3
PMCID: PMC1931583  PMID: 17608943
4.  Comparison of manual and semi-automated delineation of regions of interest for radioligand PET imaging analysis 
Background
As imaging centers produce higher resolution research scans, the number of man-hours required to process regional data has become a major concern. Comparison of automated vs. manual methodology has not been reported for functional imaging. We explored validation of using automation to delineate regions of interest on positron emission tomography (PET) scans. The purpose of this study was to ascertain improvements in image processing time and reproducibility of a semi-automated brain region extraction (SABRE) method over manual delineation of regions of interest (ROIs).
Methods
We compared 2 sets of partial volume corrected serotonin 1a receptor binding potentials (BPs) resulting from manual vs. semi-automated methods. BPs were obtained from subjects meeting consensus criteria for frontotemporal degeneration and from age- and gender-matched healthy controls. Two trained raters provided each set of data to conduct comparisons of inter-rater mean image processing time, rank order of BPs for 9 PET scans, intra- and inter-rater intraclass correlation coefficients (ICC), repeatability coefficients (RC), percentages of the average parameter value (RM%), and effect sizes of either method.
Results
SABRE saved approximately 3 hours of processing time per PET subject over manual delineation (p < .001). Quality of the SABRE BP results was preserved relative to the rank order of subjects by manual methods. Intra- and inter-rater ICC were high (>0.8) for both methods. RC and RM% were lower for the manual method across all ROIs, indicating less intra-rater variance across PET subjects' BPs.
Conclusion
SABRE demonstrated significant time savings and no significant difference in reproducibility over manual methods, justifying the use of SABRE in serotonin 1a receptor radioligand PET imaging analysis. This implies that semi-automated ROI delineation is a valid methodology for future PET imaging analysis.
doi:10.1186/1471-2385-7-2
PMCID: PMC1802071  PMID: 17261193
5.  Variation in heart rate influences the assessment of transient ischemic dilation in myocardial perfusion scintigraphy 
Background
Transient arrhythmias can affect transient ischemic dilation (TID) ratios. This study was initiated to evaluate the frequency and effect of normal heart rate change on TID measures in routine clinical practice.
Methods
Consecutive patients undergoing stress/rest sestamibi gated myocardial perfusion scintigraphy were studied (N = 407). Heart rate at the time of stress and rest imaging were recorded. TID ratios were analyzed in relation to absolute change in heart rate (stress minus rest) for subjects with normal perfusion and systolic function (Group 1, N = 169) and those with abnormalities in perfusion and/or function (Group 2, N = 238).
Results
In Group 1, mean TID ratio was inversely correlated with the change in heart rate (r = -0.47, P < 0.0001). For every increase of 10 BPM in heart rate change, the TID ratio decreased by approximately 0.06 (95% confidence interval 0.04–0.07). In Group 2, multiple linear regression demonstrated that the change in heart rate (beta = -0.25, P < 0.0001) and the summed difference score (beta = 0.36, P < 0.0001) were independent predictors of the TID ratio.
Conclusion
Normal variation in heart rate between the stress and rest components of myocardial perfusion scans is common and can influence TID ratios in patients with normal and abnormal cardiac scans.
doi:10.1186/1471-2385-7-1
PMCID: PMC1779770  PMID: 17217538
6.  Comparison of 18F SPECT with PET in myocardial imaging: A realistic thorax-cardiac phantom study 
Background
Positron emission tomography (PET) imaging with fluorine-18 (18F) Fluorodeoxyglucose (FDG) and flow tracer such as Rubidium-82 (82Rb) is an established method for evaluating an ischemic but viable myocardium. However, the high cost of PET imaging restricts its wider clinical use. Therefore, less expensive 18F FDG single photon emission computed tomography (SPECT) imaging has been considered as an alternative to 18F FDG PET imaging. The purpose of the work is to compare SPECT with PET in myocardial perfusion/viability imaging.
Methods
A nonuniform RH-2 thorax-heart phantom was used in the SPECT and PET acquisitions. Three inserts, 3 cm, 2 cm and 1 cm in diameter, were placed in the left ventricular (LV) wall to simulate infarcts. The phantom acquisition was performed sequentially with 7.4 MBq of 18F and 22.2 MBq of Technetium-99m (99mTc) in the SPECT study and with 7.4 MBq of 18F and 370 MBq of 82Rb in the PET study. SPECT and PET data were processed using standard reconstruction software provided by vendors. Circumferential profiles of the short-axis slices, the contrast and viability of the inserts were used to evaluate the SPECT and PET images.
Results
The contrast for 3 cm, 2 cm and 1 cm inserts were for 18F PET data, 1.0 ± 0.01, 0.67 ± 0.02 and 0.25 ± 0.01, respectively. For 82Rb PET data, the corresponding contrast values were 0.61 ± 0.02, 0.37 ± 0.02 and 0.19 ± 0.01, respectively. For 18F SPECT the contrast values were, 0.31 ± 0.03 and 0.20 ± 0.05 for 3 cm and 2 cm inserts, respectively. For 99mTc SPECT the contrast values were, 0.63 ± 0.04 and 0.24 ± 0.05 for 3 cm and 2 cm inserts respectively. In SPECT, the 1 cm insert was not detectable. In the SPECT study, all three inserts were falsely diagnosed as "viable", while in the PET study, only the 1 cm insert was diagnosed falsely "viable".
Conclusion
For smaller defects the 99mTc/18F SPECT imaging cannot entirely replace the more expensive 82Rb/18F PET for myocardial perfusion/viability imaging, due to poorer image spatial resolution and poorer defect contrast.
doi:10.1186/1471-2385-6-5
PMCID: PMC1634842  PMID: 17076890
7.  A statistical investigation of normal regional intra-subject heterogeneity of brain metabolism and perfusion by F-18 FDG and O-15 H2O PET imaging 
Background
The definite evaluation of the regional cerebral heterogeneity using perfusion and metabolism by a single modality of PET imaging has not been well addressed. Thus a statistical analysis of voxel variables from identical brain regions on metabolic and perfusion PET images was carried out to determine characteristics of the regional heterogeneity of F-18 FDG and O-15 H2O cerebral uptake in normal subjects.
Methods
Fourteen normal subjects with normal CT and/or MRI and physical examination including MMSE were scanned by both F-18 FDG and O-15 H2O PET within same day with head-holder and facemask. The images were co-registered and each individual voxel counts (Q) were normalized by the gloabl maximal voxel counts (M) as R = Q/M. The voxel counts were also converted to z-score map by z = (Q - mean)/SD. Twelve pairs of ROIs (24 total) were systematically placed on the z-score map at cortical locations 15-degree apart and identically for metabolism and perfusion. Inter- and intra-subject correlation coefficients (r) were computed, both globally and hemispherically, from metabolism and perfusion: between regions for the same tracer and between tracers for the same region. Moments of means and histograms were computed globally along with asymmetric indices as their hemispherical differences.
Results
Statistical investigations verified with data showed that, for a given scan, correlation analyses are expectedly alike regardless of variables (Q, R, z) used. The varieties of correlation (r's) of normal subjects, showing symmetry, were mostly around 0.8 and with coefficient of variations near 10%. Analyses of histograms showed non-Gaussian behavior (skew = -0.3 and kurtosis = 0.4) of metabolism on average, in contrast to near Gaussian perfusion.
Conclusion
The co-registered cerebral metabolism and perfusion z maps demonstrated regional heterogeneity but with attractively low coefficient of variations in the correlation markers.
doi:10.1186/1471-2385-6-4
PMCID: PMC1550222  PMID: 16836759
8.  Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation 
Background
Coronary atherosclerosis and its thrombotic complications are the major cause of mortality and morbidity throughout the industrialized world. Thrombosis on disrupted atherosclerotic plaques plays a key role in the onset of acute coronary syndromes. Macrophages density is one of the most critical compositions of plaque in both plaque vulnerability and thrombogenicity upon rupture. It has been shown that macrophages have a high uptake of 18F-FDG (FDG). We studied the correlation of FDG uptake with histopathological macrophage accumulation in atherosclerotic plaques in a rabbit model.
Methods
Atherosclerosis was induced in rabbits (n = 6) by a combination of atherogenic diet and balloon denudation of the aorta. PET imaging was performed at baseline and 2 months after atherogenic diet and coregistered with magnetic resonance (MR) imaging. Normal (n = 3) rabbits served as controls. FDG uptake by the thoracic aorta was expressed as concentration (μCi/ml) and the ratio of aortic uptake-to-blood radioactivity. FDG uptake and RAM-11 antibody positive areas were analyzed in descending aorta.
Results
Atherosclerotic aortas showed significantly higher uptake of FDG than normal aortas. The correlation of aortic FDG uptake with macrophage areas assessed by histopathology was statistically significant although it was not high (r = 0.48, p < 0.0001). When uptake was expressed as the ratio of aortic uptake-to-blood activity, it correlated better (r = 0.80, p < 0.0001) with the macrophage areas, due to the correction for residual blood FDG activity.
Conclusion
PET FDG activity correlated with macrophage content within aortic atherosclerosis. This imaging approach might serve as a useful non-invasive imaging technique and potentially permit monitoring of relative changes in inflammation within the atherosclerotic lesion.
doi:10.1186/1471-2385-6-3
PMCID: PMC1479805  PMID: 16725052
9.  Prognostic utility of sestamibi lung uptake does not require adjustment for stress-related variables: A retrospective cohort study 
Background
Increased 99mTc-sestamibi stress lung-to-heart ratio (sLHR) has been shown to predict cardiac outcomes similar to pulmonary uptake of thallium. Peak heart rate and use of pharmacologic stress affect the interpretation of lung thallium uptake. The current study was performed to determine whether 99mTc-sestamibi sLHR measurements are affected by stress-related variables, and whether this in turn affects prognostic utility.
Methods
sLHR was determined in 718 patients undergoing 99mTc-sestamibi SPECT stress imaging. sLHR was assessed in relation to demographics, hemodynamic variables and outcomes (mean follow up 5.6 ± 1.1 years).
Results
Mean sLHR was slightly greater in males than in females (P < 0.01) and also showed a weak negative correlation with age (P < 0.01) and systolic blood pressure (P < 0.01), but was unrelated to stress method or heart rate at the time of injection. In patients undergoing treadmill exercise, sLHR was also positively correlated with peak workload (P < 0.05) but inversely with double product (P < 0.05). The combined explanatory effect of sex, age and hemodynamic variables on sLHR was less than 10%. The risk of acute myocardial infarction (AMI) or death increased by a factor of 1.7–1.8 for each SD increase in unadjusted sLHR, and was unaffected by adjustment for sex, age and hemodynamic variables (hazard ratios 1.6–1.7). The area under the ROC curve for the unadjusted sLHR was 0.65 (95% CI 0.59–0.71, P < 0.0001) and was unchanged for the adjusted sLHR (0.65, 95% CI 0.61–0.72, P < 0.0001).
Conclusion
Stress-related variables have only a weak effect on measured sLHR. Unadjusted and adjusted sLHR provide equivalent prognostic information for prediction of AMI or death.
doi:10.1186/1471-2385-6-2
PMCID: PMC1444924  PMID: 16571123
10.  Frequency and severity of myocardial perfusion abnormalities using Tc-99m MIBI SPECT in cardiac syndrome X 
Background
Cardiac syndrome X is defined by a typical angina pectoris with normal or near normal (stenosis <40%) coronary angiogram with or without electrocardiogram (ECG) change or atypical angina pectoris with normal or near normal coronary angiogram plus a positive none-invasive test (exercise tolerance test or myocardial perfusion scan) with or without ECG change. Studies with myocardial perfusion imaging on this syndrome have indicated some abnormal perfusion scan. We evaluated the role of myocardial perfusion imaging (MPI) and also the severity and extent of perfusion abnormality using Tc-99m MIBI Single Photon Emission Computed Tomography (SPECT) in these patients.
Methods
The study group consisted of 36 patients with cardiac syndrome X. The semiquantitative perfusion analysis was performed using exercise Tc-99m MIBI SPECT. The MPI results were analyzed by the number, location and severity of perfusion defects.
Results
Abnormal perfusion defects were detected in 13 (36.10%) cases, while the remaining 23 (63.90%) had normal cardiac imaging. Five of 13 (38.4%) abnormal studies showed multiple perfusion defects. The defects were localized in the apex in 3, apical segments in 4, midventricular segments in 12 and basal segments in 6 cases. Fourteen (56%) of all abnormal segments revealed mild, 7(28%) moderate and 4 (16%) severe reduction of tracer uptake. No fixed defects were identified. The vessel territories were approximately the same in all subjects. The Exercise treadmill test (ETT) was positive in 25(69%) and negative in 11(30%) patients. There was no consistent pattern as related to the extent of MPI defects or exercise test results.
Conclusion
Our study suggests that multiple perfusion abnormalities with different levels of severity are common in cardiac syndrome X, with more than 30 % of these patients having at least one abnormal perfusion segment. Our findings suggest that in these patients microvascular angina is probably more common than is generally believed.
doi:10.1186/1471-2385-6-1
PMCID: PMC1402267  PMID: 16503964
11.  Relationship of 99mtechnetium labelled macroaggregated albumin (99mTc-MAA) uptake by colorectal liver metastases to response following Selective Internal Radiation Therapy (SIRT) 
Background
SIRT is an emerging treatment for liver tumours which relies on the selective uptake by tumour of 90Y microspheres following hepatic arterial injection. Response rates of around 90% are reported. Hepatic arterial injection of MAA gives an indication of the expected distribution of 90Y microspheres within the liver. This study sought to determine if the MAA scan could be predictive of subsequent tumour response.
Methods
58 patients with colorectal hepatic metastases received SIRT. All had pre-treatment MAA planar images and CT scans which were retrospectively reviewed. Tumours were qualitatively considered "cold", "equivocal" or "hot" based on MAA uptake and the ratio of uptake in tumour and normal liver tissue was calculated (TNR). Following SIRT (which included the administration of hepatic arterial Angiotensin 2) tumour response was assessed by CEA changes one to two months after treatment and by serial CT.
Results
Uptake was classified as "hot" in 37 patients (Group 1) and "equivocal" or "cold" in 21 (Group 2). CEA levels fell dramatically in over 90% of patients. The falls were not significantly different between the groups. There was no correlation between TNR and tumour response based on CEA changes (r2 = 0.004). CT responses after 3 months were not different in the 2 Groups.
Conclusion
The pattern of MAA uptake by colorectal liver tumours after arterial injection is not a predictor of tumour response after treatment by SIRT. The results suggest the doses of 90Y microspheres used may be greater than is necessary.
doi:10.1186/1471-2385-5-7
PMCID: PMC1360059  PMID: 16375764
12.  A preliminary study of neuroSPECT evaluation of patients with post-traumatic smell impairment 
Background
Most olfactory testings are subjective and since they depend upon the patients' response, they are prone to false positive results. The aim of this study was to use quantitative brain perfusion SPECT in order to detect possible areas of brain activation in response to odorant stimulation in patients with post-traumatic impaired smell in comparison to a group of normal subjects.
Methods
Fourteen patients with post-traumatic impaired smell and ten healthy controls were entered in this prospective study. All subjects underwent brain SPECT after intravenous injection of 740-MBq 99mTc-ECD and 48 hours later, the same procedure was repeated following olfactory stimulus (vanilla powder).
Results
In most of seven regions of interest (Orbital Frontal Cortex, Inferior Frontal Pole, Superior Frontal Pole, Posterior Superior Frontal Lobe, Parasagittal Area, Occipital Pole, and Cerebellar area) the post-stimulation quantitative values show increased cortical perfusion being more pronounced in normal volunteers than the anosmic patients (except cerebellar areas and the right occipital pole). Maximal activation was observed in orbitofrontal regions (right+ 25.45% and left +25.47%).
Conclusion
Brain SPECT is a valuable imaging technique in the assessment of post-traumatic anosmia and could be competitive as an alternative to other imaging techniques, especially when functional MRI is unavailable or unsuitable. However, this procedure may benefit from complementary MRI or CT anatomical imaging.
doi:10.1186/1471-2385-5-6
PMCID: PMC1314885  PMID: 16313675
13.  Hydrophilic and lipophilic radiopharmaceuticals as tracers in pharmaceutical development: In vitro – In vivo studies 
Background
Scintigraphic studies have been performed to assess the release, both in vitro and in vivo, of radiotracers from tablet formulations. Four different tracers with differing physicochemical characteristics have been evaluated to assess their suitability as models for drug delivery.
Methods
In-vitro disintegration and dissolution studies have been performed at pH 1, 4 and 7. In-vivo studies have been performed by scintigraphic imaging in healthy volunteers. Two hydrophilic tracers, (99mTc-DTPA) and (99mTc-MDP), and two lipophilic tracers, (99mTc-ECD) and (99mTc-MIBI), were used as drug models.
Results
Dissolution and disintegration profiles, differed depending on the drug model chosen. In vitro dissolution velocity constants indicated a probable retention of the radiotracer in the formulation. In vivo disintegration velocity constants showed important variability for each radiopharmaceutical. Pearson statistical test showed no correlation between in vitro drug release, and in vivo behaviour, for 99mTc-DTPA, 99mTc-ECD and 99mTc-MIBI. High correlation coefficients were found for 99mTc-MDP not only for in vitro dissolution and disintegration studies but also for in vivo scintigraphic studies.
Conclusion
Scintigraphic studies have made a significant contribution to the development of drug delivery systems. It is essential, however, to choose the appropriate radiotracers as models of drug behaviour. This study has demonstrated significant differences in release patterns, depending on the model chosen. It is likely that each formulation would require the development of a specific model, rather than being able to use a generic drug model on the basis of its physicochemical characteristics.
doi:10.1186/1471-2385-5-5
PMCID: PMC1274329  PMID: 16232323
14.  Planar Tc99m – sestamibi scintimammography should be considered cautiously in the axillary evaluation of breast cancer protocols: Results of an international multicenter trial 
Background
Lymph node status is the most important prognostic indicator in breast cancer in recently diagnosed primary lesion. As a part of an interregional protocol using scintimammography with Tc99m compounds, the value of planar Tc99m sestamibi scanning for axillary lymph node evaluation is presented. Since there is a wide range of reported values, a standardized protocol of planar imaging was performed.
Methods
One hundred and forty-nine female patients were included prospectively from different regions. Their mean age was 55.1 ± 11.9 years. Histological report was obtained from 2.987 excised lymph nodes from 150 axillas. An early planar chest image was obtained at 10 min in all patients and a delayed one in 95 patients, all images performed with 740–925 MBq dose of Tc99m sestamibi. Blind lecture of all axillary regions was interpreted by 2 independent observers considering any well defined focal area of increased uptake as an involved axilla. Diagnostic values, 95% confidence intervals [CI] and also likelihood ratios (LR) were calculated.
Results
Node histology demonstrated tumor involvement in 546 out of 2987 lymph nodes. Sestamibi was positive in 30 axillas (25 true-positive) and negative in 120 (only 55 true-negative). The sensitivity corresponded to 27.8% [CI = 18.9–38.2] and specificity to 91.7% [81.6–97.2]. The positive and negative LR were 3.33 and 0.79, respectively. There was no difference between early and delayed images. Sensitivity was higher in patients with palpable lesions.
Conclusion
This work confirmed that non tomographic Tc99m sestamibi scintimammography had a very low detection rate for axillary lymph node involvement and it should not be applied for clinical assessment of breast cancer.
doi:10.1186/1471-2385-5-4
PMCID: PMC1199526  PMID: 16048648
15.  Use of segmented CT transmission map to avoid metal artifacts in PET images by a PET-CT device 
Background: Attenuation correction is generally used to PET images to achieve count rate values independent from tissue densities. The goal of this study was to provide a qualitative comparison of attenuation corrected PET images produced by a PET-CT device (CT, 120 kV, 40 mAs, FOV 600 mm) with and without segmentation of transmission data (ACseg+ and ACseg-respectively). Methods: The reconstructed images were compared to attenuation corrected images obtained with a high-energy transmission source (Cs-137 – 662 keV).
Thirty oncologic patients were studied using CT and 137Cs for attenuation correction. All image data were acquired using the Gemini PET-CT scanner (Philips Medical Systems). It is an open PET-CT system that consists of the MX8000 multislice CT and the Allegro PET scanner arranged in a separable configuration. Images with ACseg+ and ACseg- were analyzed simultaneously in coronal, sagittal and transaxial planes. Two nuclear medicine physicians reviewed the image sets. Results: The image quality in the area of metal implants was better with ACseg+ than ACseg-, without metal induced artifacts generally observed in CT corrected images. Further the images with ACseg+ were qualitatively comparable to those obtained with 137Cs attenuation correction. Conclusions: In case of metal implants, PET studies corrected by CT should preferably use the ACseg+ method to avoid the image artifacts.
doi:10.1186/1471-2385-5-3
PMCID: PMC1164418  PMID: 15953395
16.  Comparison of SPECT bone scintigraphy with MRI for diagnosis of meniscal tears 
Background
Scintigraphy has been considered as competitive to MRI, but limited data are available on the accuracy of single photon emission tomography (SPECT) compared with MRI for the assessment of meniscal tears. Our objective was to assess the value of SPECT in comparison to MRI.
Methods
Between January 2003 and March 2004, sixteen patients were studied with both modalities and the accuracy rates of SPECT scan results, and MRI findings in the diagnosis of meniscal tears were compared. Arthroscopy was the gold standard.
Results
The respective sensitivity rate, specificity rate, and positive and negative predictive accuracies of MRI were 89%, 94%, 93%, and 79% and for SPECT those were 78%, 94%, 94%, and 88%. There was good agreement on the presence or absence of tears between two modalities (κ statistic = 0.699).
Conclusion
SPECT and MRI are both valuable imaging techniques. SPECT is a useful alternative when MRI is unavailable or unsuitable and it is beneficial when more possible accuracy is desired (such as when MRI results are either inconclusive or conflict with other clinical data).
doi:10.1186/1471-2385-5-2
PMCID: PMC1090590  PMID: 15831098
17.  Sodium pertechnetate (Na99mTcO4) biodistribution in mice exposed to cigarette smoke 
Background
The biological effects of cigarette smoke are not fully known. To improve our understanding of the action of various chemical agents, we investigated the biodistribution of sodium pertechnetate (Na99mTcO4) in mice exposed to cigarette smoke.
Methods
Fifteen BALB/c male mice were exposed to the smoke of nine whole commercial cigarettes per day, 3 times/day, for up to 10 days to whole body exposure in a chamber. A control group of 5 BALB/c male mice was sham-smoked. One day later, the exposed and control groups of mice received (7.4 MBq/0.3 ml) of Na99mTcO4 before being killed at 30 min. Bones, brain, heart, intestine, kidney, liver, lungs, muscle, pancreas, spleen, stomach, testis and thyroid were weighed and these organs and blood radioactivity recorded with a gamma counter. The percentage per gram of tissue of injected dose (%ID/g) was determined for each organ.
Results
Cigarette smoke significantly decreased (p < 0.05) the %ID/g in red blood cells, bone, kidney, lung, spleen, stomach, testis and thyroid of the exposed mice.
Conclusion
The toxic effects of cigarette smoke reduced the Na99mTcO4 biodistribution.
doi:10.1186/1471-2385-5-1
PMCID: PMC1090589  PMID: 15823206
18.  Evaluation of the clinical value of bone metabolic parameters for the screening of osseous metastases compared to bone scintigraphy 
Background
Bone metastases are common in many types of cancer. As screening methods different imaging modalities are available. A new approach for the screening of osseous metastases represents the measurement of bone metabolic markers. Therefore aim of this study was to evaluate the usefulness of the determination of bone metabolic markers aminoterminal propeptide of type I procollagen (PINP, osteoblastic activity) and the carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP, osteoclastic activity) for the detection of bone metastases associated with other malignancies.
Methods
88 patients aged 21 – 82 years with malignant tumors were prospectively studied. The serum concentrations of PINP and ICTP were measured and compared to the results of bone scintigraphy, radiological bone series, CT, MRI and clinical follow-up.
Results
Osseous metastases were found in 21 patients. 19 of them were correctly identified by bone scintigraphy (sensitivity: 90%). For bone metabolic markers results were as follows: ICTP sensitivity: 71%, specificity: 42%; PINP sensitivity: 24%, specificity: 96%.
Conclusions
As markers of bone metabolism PINP and ICTP showed low sensitivity and/or specificity for the detection of osseous metastases. The presented markers did not seem to be sufficient enough to identify patients with bone metastases or to replace established screening methods.
doi:10.1186/1471-2385-4-3
PMCID: PMC539349  PMID: 15579208
19.  The hazards of lack of co-registration of ictal brain SPECT with MRI: A case report of sinusitis mimicking a brainstem seizure focus 
Background
Single photon emission computed tomography (SPECT) following injection of radiotracer during a seizure is known as ictal SPECT. Comparison of an ictal SPECT study to a baseline or interictal study can aid identification of a seizure focus.
Case presentation
A young woman with encephalitis and refractory seizures underwent brain SPECT during a period of frequent seizure-like episodes, and during a seizure-free period. A focal area of increased radiotracer uptake present only when she was experiencing frequent seizure-like episodes was originally localized to the brainstem, but with later computerized co-registration of SPECT to MRI, was found to lie outside the brain, in the region of the sphenoid sinus.
Conclusion
Low-resolution SPECT images present difficulties in interpretation, which can be overcome through co-registration to higher-resolution structural images.
doi:10.1186/1471-2385-4-2
PMCID: PMC535895  PMID: 15569392
20.  188Re radiopharmaceuticals for radiosynovectomy: evaluation and comparison of tin colloid, hydroxyapatite and tin-ferric hydroxide macroaggregates 
Background
Radiosynovectomy is a therapy used to relieve pain and inflammation from rheumatoid arthritis and related diseases. In this study three 188Re particulate compounds were characterized according to their physico-chemical properties and their biological behavior in rabbits. The results were compared in order to establish which was the radiopharmaceutical that better fits the requirements of this kind of radiotherapy.
Methods
Three radiopharmaceutical formulations, tin colloid, hydroxyapatite particles (HA) and ferric hydroxide macroaggregates coated with tin colloid (FHMA), were physically characterized (number, volume and surface of the particles). For this purpose laser diffraction methodology was used. To evaluate cavity leakage of activity the following studies in New Zealand rabbits were performed: scintigraphic images for 48 hr after intraarticular injection of each radiopharmaceutical, biodistribution at 48 hr and urine samples collection during the first 24 hr post-radiopharmaceutical administration.
Results
Labeling procedures for 188Re-HA and 188Re-Sn-FHMA were labour intensive while 188Re-Sn was easily prepared. Furthermore, 188Re-Sn colloid offered the greatest surface area in the 2–10 microm range and was obtained with a radiochemical purity over 95%, while percentage of bound activity for 188Re-HA and 188Re-Sn-FHMA were 55% and 92% respectively. Stability was verified for the three radiopharmaceuticals for 24 hr. Scintigraphic studies and biodistribution in rabbits after intraarticular administration of the radiopharmaceuticals showed relevant activity only in the knee, this being over 90% of the residual activity in the whole body at 48 hr in every case. Renal elimination of 188Re-Sn colloid and 188Re-Sn-FHMA was detected by activity measurements in urine samples, during the first 12 hr post-radiopharmaceutical injection.
The percentage of activity retained in the knee was 69.1% for 188Re-Sn colloid, 55.1% for 188Re-Sn-FHMA and 33.6% for 188Re-HA.
Conclusion
The 188Re-Sn colloid was easy to prepare, minimum facilities were required, was stable for 24 hr and showed minimal leakage from the joint after intraarticular injection into the rabbit's knee. Furthermore, 188Re-Sn colloid has greater retention in the knee when it is compared with the other radiopharmaceuticals, so it could provide the best therapeutic effect/absorbed dose ratio for the patient.
doi:10.1186/1471-2385-4-1
PMCID: PMC373254  PMID: 15040807
21.  Comparison of Technetium-99m-MIBI imaging with MRI for detection of spine involvement in patients with multiple myeloma 
Background
Recently, radiopharmaceutical scanning with Tc-99m-MIBI was reported to depict areas with active bone disease in multiple myeloma (MM) with both high sensitivity and specificity. This observation was explained by the uptake of Tc-99m-MIBI by neoplastic cells. The present investigation evaluates whether Tc-99m-MIBI imaging and magnetic resonance imaging (MRI) perform equally well in detecting myelomatous bone marrow lesions.
Methods
In 21 patients with MM, MRIs of the vertebral region TH12 to S1 and whole body scans with Tc-99m-MIBI were done.
Results
Tc-99m-MIBI scanning missed bone marrow infiltration in 43 of 87 vertebrae (50.5%) in which MRI showed neoplastic bone marrow involvement. In patients with disease stage I+II, Tc-99m-MIBI scanning was negative in all of 24 vertebrae infiltrated according to MRI. In patients with disease stage III, Tc-99m-MIBI scanning detected 44 of 63 (70%) vertebrae involved by neoplastic disease.
Conclusion
Tc-99m-MIBI scanning underestimated the extent of myelomatous bone marrow infiltration in the spine, especially in patients with low disease stage.
doi:10.1186/1471-2385-3-2
PMCID: PMC317308  PMID: 14670090
22.  Assessment of diffuse Lewy body disease by 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) 
Background
Lewy body disease is, after Alzheimer's disease, the second most common cause of senile degenerative dementia with progressive cognitive deterioration, fluctuation of cognitive and motoric functions and psychotic symptoms. It is characterized histologically by the occurrence of Lewy bodies in allocortical, neocortical and subcortical structures. The aim of this study was to measure the cortical glucose metabolism using FDG PET (2-[18F]fluoro-2-deoxy-D-glucose position emission tomography) compared to normal subjects.
Patients and Methods
Five patients (5 m, mean age 75 y) with clinically suspected diffuse Lewy body disease (DLB) were studied with FDG PET. PET studies of the head were performed with a Siemens ECAT-ART PET-scanner with attenuation correction using 137-Cs point sources.
Results
We found the same distribution pattern of diffuse glucose hypometabolism in the entire cortical region with relative sparing of the primary sensory-motor cortex in all the patients. The few cases reported in the literature so far describe findings similar to ours.
Conclusion
The pattern of diffuse glucose hypometabolism in the entire cortex including the occipital region seems to be a typical feature of DLB that is distinctive from dementia of Alzheimer's disease.
doi:10.1186/1471-2385-3-1
PMCID: PMC151666  PMID: 12625839
Dementia; FDG PET; Lewy body disease
23.  Physico-chemical characterisation and biological evaluation of 188-Rhenium colloids for radiosynovectomy 
Background
Radiosynovectomy is a type of radiotherapy used to relieve pain and inflammation from rheumatoid arthritis. In this study, 188-Rhenium (188Re) colloids were characterized by physical and biological methodologies. This was used to assess which parameters of the kit formulation would be the basis in the development of a more effective radiopharmaceutical for synovectomy. Intraarticular injection in knees of rabbits assessed cavity leakage of activity.
Methods
The physical characteristics of tin (Sn) and sulphur (S) colloids were determined to assess the formulation with suitable properties. Particles were grouped in three ranges for analyzing their distribution according to their number, volume and surface. The ideal particle size range was considered to be from 2 to 10 microns. Membrane filtration and laser diffraction characterization methodologies were used.
Results
While membrane filtration could give misleading data, laser diffraction proportions more reliable results. The Sn colloid showed a better distribution of particle volume and surface than S colloid, in the 2 to 10 microns range. The 188Re-Sn colloid was obtained with a radiochemical purity higher than 95% after 30 minutes of autoclaving. While Sn colloid kit stability was verified for 60 days, the 188Re-Sn preparation was stable in the first 24 hrs. No significant intrabatch variability (n = 3) was detected. Biodistribution and scintigraphic studies in rabbits after intraarticular injection showed relevant activity only in knee, being 90% at 48 hours.
Conclusion
The 188Re-Sn colloid is easy to prepare, is stable for 24 hours and shows minimal cavity leakage after intraarticular injection into rabbit knees, suggesting this radiotherapeutical agent has suitable physical properties for evaluation for joint treatment in humans.
doi:10.1186/1471-2385-2-1
PMCID: PMC134460  PMID: 12379158
24.  Re-HEDP : pharmacokinetic characterization, clinical and dosimetric evaluation in osseous metastatic patients with two levels of radiopharmaceutical dose 
Background
A study for pain relief therapy with 188Re-HEDP was done in patients with bone metastases secondary to breast and prostate cancer.
Materials and Methods
Patients received 1.3 or 2.2 GBq, in single or multiple doses. Platelets, white and red cells were evaluated during 11 weeks. Pharmacokinetic characterization was done from blood and urine samples for 5 patients along 24 hours. Urinary excretion was evaluated in other 16 patients during 6 hours. Bone uptake was estimated as remaining activity in whole body. Scintigraphic images were acquired at 2 and 24 hs post-administration. Absorbed dose in bone marrow was estimated with Mirdose3. Analgesics intake and pain score were daily recorded. Tumour markers (PSA, and Tn-structure) were monitored in 9 patients during 4 to 6 months. Single doses of low activity (1.3 GBq) were given to twelve patients. Nine patients received multiple doses.
Results
All except one patient had normal levels of platelets, white and red cells. Remaining dose in blood at 2 hours was 9%. Urinary elimination was 58%. Bone uptake at 24 hours was 43% (mean value; n = 5). No changes of the haematological parameters were detected along follow-up period. Pain relief was evidenced by decrease or supression of opioid analgesic and by subjective index. PSA showed a decrease in prostate cancer patients (n = 4). Tn-structure showed a significant increase after 4 to 8 months.
Conclusion
Single or multiple dose scheme could be safely used, with administered activity of 188Re-HEDP up to 60 mCi, with low bone marrow absorbed doses.
doi:10.1186/1471-2385-1-2
PMCID: PMC60657  PMID: 11734069
25.  A mathematical model of optimized radioiodine-131 therapy of Graves' hyperthyroidism 
Background
The current status of radioiodine-131 (RaI) dosimetry for Graves' hyperthyroidism is not clear. Recurrent hyperthyroidism and iatrogenic hypothyroidism are two problems which interact such that trying to solve one leads to exacerbation of the other. Optimized RaI therapy has therefore begun to be defined just in terms of early hypothyroidism (ablative therapy) as physicians have given up on reducing hypothyroidism.
Methods
Optimized therapy is evaluated both in terms of the greatest separation of cure rate from hypothyroidism rate (non-ablative therapy) or in terms of early hypothyroidism (ablative therapy) by mathematical modeling of outcome after radioiodine and critically discussing the three common methods of RaI dosing for Graves' disease.
Results
Cure follows a logarithmic relationship to activity administered or absorbed dose, while hypothyroidism follows a linear relationship. The effect of including or omitting factors in the calculation of the administered I–131 activity such as the measured thyroid uptake and effective half-life of RaI or giving extra compensation for gland size is discussed.
Conclusions
Very little benefit can be gained by employing complicated methods of RaI dose selection for non-ablative therapy since the standard activity model shows the best potential for cure and prolonged euthyroidism. For ablative therapy, a standard MBq/g dosing provides the best outcome in terms of cure and early hypothyroidism.
doi:10.1186/1471-2385-1-1
PMCID: PMC56607  PMID: 11570980

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