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Objective: Estimation of myocardial blood flow (MBF) and coronary flow reserve (CFR) by SPECT myocardial perfusion imaging (MPI) remains challenging. Our aim was to approximate MBF and CFR by quantifying the absolute Tc-99m tetrofosmin retention in the myocardium via gated-SPECT/CT MPI., Methods: Tracer retention was calculated on the basis of the microsphere kinetic model and served as an index of MBF at stress and rest (sMBFi, rMBFi). CFR was given by the sMBFi/rMBFi ratio. A planar first-pass acquisition during dipyridamole stress and at rest provided the data for tracer input determination. The input was represented by the integral of a gamma variate fitted on the time-activity curve of the left ventricle. Gated-SPECT/CT was performed 1 h post tracer injection and myocardial activity was measured in attenuation-corrected transaxial slices by a threshold VOI. The input was also compensated for tissue attenuation by measuring the distance from the centre of the left ventricle to the body surface on fused SPECT/CT slices. Input and uptake results were adjusted for planar-SPECT counting geometry differences by the aid of a phantom experiment. Thirty-nine subjects with low probability of coronary artery disease (CAD), age lower than 75 years and normal MPI (control group) were compared with 57 patients with documented CAD (CAD group)., Results: CFR and sMBFi values of CAD patients (1.39 ± 0.37 and 1.42 ± 0.35 ml/min/g) were considerably lower (p < 0.0001) than controls (1.68 ± 0.25 and 1.72 ± 0.37 ml/min/g). Significant difference in CFR (p = 0.03) was also noted between CAD patients with normal MPI (1.48 ± 0.38) and controls. However, sMBFi managed to discriminate certain CAD subgroups (normal MPI/ischemia/scar/scar and ischemia) more efficiently than CFR. Maximum heart rate-blood pressure product (RPP) during stress was an independent predictor of sMBFi and CFR. The other independent CFR correlates were resting RPP and diabetes mellitus, while sMBFi was associated with age, sex, smoking, and stress perfusion defects., Conclusions: Despite the low myocardial extraction fraction of Tc-99m tetrofosmin, an approximation of MBF and CFR is feasible with gated-SPECT/CT MPI. These flow indices together were able to discriminate CAD patients from controls and stratify different patient subgroups.

Objective: Previous studies indicate that the quality of single photon emission tomography/computed tomography (SPET/CT) myocardial perfusion imaging (MPI) is degraded by even mild transmission-emission misregistrations. The purpose of the current study was to investigate the impact of SPET/CT misalignment on the interpretation of MPI and examine the value of a commercial software application for registration correction., Subjects and Methods: A total of 255 technetium-99m ((99m)Tc)-tetrofosmin stress/rest MPI examinations in 150 patients were reviewed for SPET/CT misalignment. After registration correction by the software, images were reassessed for interpretation differences from the misregistered study. The diagnostic benefit of reregistration was determined by taking into account the non-attenuation compensated image pattern, combined stress-rest evaluation, gated-SPET data and patient's history. In a phantom experiment and in 3 representative clinical cases, SPET/CT misalignment was purposely created by the software by sequential slice shifts and its effect was evaluated quantitatively., Results: Misregistration ≥1 pixel in at least one direction was observed in 24% of studies. Interpretation of MPI changed after registration correction in 11% of cases with misalignment <1 pixel, in 18% with 1-2 and in 73% with ≥2 pixels. The diagnostic information seemed to improve after registration correction in 58% of studies irrespective of the degree of misregistration. Software-simulated misregistration had dissimilar effects in the phantom and the 3 selected clinical cases., Conclusions: The impact of SPET/CT misregistration on MPI interpretation although influenced by the degree and direction of slice misplacement, it is also case-specific and hardly predictable. Registration restoration by the software seems worthwhile regardless of misregistration magnitude.

Background: Previous studies advocate the use of attenuation correction in myocardial perfusion scintigraphy (MPS) for patient risk stratification., Methods: Six-hundred and thirty-seven unselected patients underwent Tl-201 MPS by a hybrid SPECT/CT system. Attenuation-corrected (AC) and non-corrected (NAC) images were interpreted blindly and summed stress scores (SSS) were calculated. Study endpoints were all-cause mortality and the composites of death/non-fatal acute myocardial infarction (AMI) and death/AMI/late revascularization., Results: During a follow-up of 42.3 ± 12.8 months 24 deaths, 13 AMIs and 28 revascularizations were recorded. SSS groups formed according to event rate distribution across SSS values were: 0-4, 5-13, >13 for NAC and 0-2, 3-9, >9 for AC. Kaplan-Meier functions were statistically significant between NAC SSS groups for all study endpoints. AC discriminated only between SSS 0-2 and >9 for death/AMI and between 0-2 and 3-9 for death/AMI/revascularization. In the univariate Cox regression abnormal NAC (SSS > 4) was accompanied with much higher hazards ratios than abnormal AC (SSS > 2). In the multivariate model abnormal AC yielded no significance for either endpoint whereas abnormal NAC proved independent from other covariates for the composite endpoints., Conclusion: Our results challenge the effectiveness of CT-based AC for risk stratification of patients referred for MPS.

Objective: To investigate the potential role of Tc-99m depreotide (Tc-DEPR) in the preoperative lymph node (N) staging of non-small-cell lung cancer (NSCLC)., Methods: Sixty-one patients with NSCLC at the potentially operable stage were enrolled and underwent scintigraphy before surgery (n=56) or mediastinoscopy (n=5). Imaging was performed with a hybrid single photon emission computed tomography/computed tomography (SPECT/CT) system. Depreotide uptake in N stations was evaluated visually and semi-quantitatively and compared to histology. Quantification was carried out in attenuation-corrected SPECT slices. Different sites of normal uptake were used as a reference for comparison with lesional uptake. Receiver operating characteristic analysis was employed to identify the most preferable reference area and the cut-off best discriminating disease-free from disease-involved lymph nodes., Results: With reference to 53 Ν1 hilar and 147 Ν2/Ν3 sampled stations, sensitivity of scintigraphy by visual interpretation was 100 and 94%, specificity 43 and 59% and accuracy 55 and 67%, respectively. No patient was down-staged, but 52% were incorrectly up-staged and 44% were misclassified as inoperable. Compared to scintigraphy, preoperative contrast-enhanced diagnostic CT demonstrated lower sensitivity (36% for hilar and 73% for N2/N3 stations), higher specificity (79 and 75%) and similar accuracy (70 and 75%). Regarding the ultimate N-stage and the prediction of surgical disease, diagnostic CT was wrong in 51 and 34% of cases. Dichotomy of quantitative scintigraphic data by the use of certain N-to-spine ratio cut-offs resulted in a significant increase of specificity (76% for hilar and 89% for N2/N3 stations), while sensitivity remained high (82% in both circumstances) and accuracy for Ν2/Ν3 stations was substantially improved (88%). By this quantitative approach, misclassifications as to the N-stage and patient operability (25 and 16%) were considerably less than that of visual Tc-DEPR and diagnostic CT interpretations., Conclusion: Tc-99m depreotide SPECT/CT seems to have a role in the N-staging of NSCLC, mainly because of its high sensitivity and negative predictive value. Quantification of uptake can improve specificity, at a low cost of sensitivity. If F-18 fluoro-deoxyglucose positron emission tomography is not available, this method may be used as a surrogate to conventional staging modalities.

Introduction: Resistance to chemotherapy poses a major problem in cancer patients. Although of multifactorial origin, some of the implicated mechanisms also interfere with (99m)Tc-MIBI uptake and retention in cancer cells. The aim of the current study was to investigate the prognostic value of baseline (99m)Tc-MIBI imaging in lymphoma., Methods: (99m)Tc-MIBI SPECT was performed in 16 patients with Hodgkin lymphoma and 31 with non-Hodgkin lymphoma (NHL) before chemotherapy initiation. Early (20 minutes), late (120 minutes) tumor-to-background (T/B) ratios, and 2-hour (99m)Tc-MIBI washout were calculated. Follow-up data were obtained for a period of 45.5 ± 23.5 months. Study end points were response to first-line chemotherapy, lymphoma-related death (LRD), and time to disease progression., Results: Of the scintigraphic indices examined, the late T/B ratio correlated best with study end points. A cutoff value of 1.8 determined by receiver operating characteristic analysis discriminated poor from good response and LRD from survival with an accuracy of 87% and 81%, respectively. Kaplan-Meier survivor functions separated by this cutoff differed significantly for both time to disease progression and LRD (P = 0.0001 and P = 0.0015). In the Cox proportional hazards model, the late T/B ratio proved to have an independent and incremental value over clinical prognostic factors (age, lymphoma type, Ann Arbor stage, lactate dehydrogenase levels) and, in NHL patients, over the international prognostic index. Patients with high international prognostic index score could be further stratified into different prognostic categories., Conclusion: The current study indicates that baseline (99m)Tc-MIBI SPECT can provide useful prognostic information in patients with lymphoma, particularly NHL, regarding therapy response and final outcome.

Purpose: The prognostic value of electrocardiographic (ECG) ST-segment depression during vasodilator stress testing in patients with normal myocardial perfusion scintigraphy (MPS) is based on retrospective studies with controversial results. Moreover, the true incidence of obstructive coronary artery disease (CAD) in these patients is unknown., Methods: During a 33-month period, all consecutive patients referred for MPS were prospectively evaluated for interpretable ST-segment depression ≥ 1 mm during vasodilator stress testing. Of 1,687 patients with normal MPS and without known CAD, 109 (100 women) aged 65.2 ± 9.2 years demonstrated ST-segment shifts and formed the ECG-positive group. The pretest probability of CAD was low in 56%, intermediate in 39% and high in 5%. They were advised to proceed to coronary angiography. An equal number of patients with normal MPS and no ECG abnormalities matched for CAD predisposing factors comprised the control group. Follow-up of both groups was accomplished through a telephone interview., Results: Fifty-two patients from the ECG-positive group (48%) consented to coronary angiography. Six (11.5%) had obstructive CAD (≥50% lumen stenosis), one with left main artery disease, while three required revascularization. Follow-up was complete in 99 ECG-positive patients for a period of 20.6 ± 8.9 months. One hard event (non-fatal myocardial infarction) and one soft event (revascularization) were observed. No event was recorded in the control group., Conclusion: In patients with low-intermediate risk of CAD, "ischaemic" ECG changes during vasodilator stress combined with normal MPS are encountered mostly in women and are associated with a low prevalence of significant CAD and a low cardiac event rate.

Objective: Previous studies have demonstrated the feasibility of targeting lymphoma lesions with somatostatin receptor binding agents, mainly with In-111-pentetreotide. In the present work another somatostatin analog, Tc-99m depreotide, is investigated., Methods: One-hundred and six patients, 47 with Hodgkin's (HL) and 59 with various types of non-Hodgkin's lymphoma (NHL), were imaged with both Tc-99m depreotide and Ga-67 citrate. Planar whole-body and single photon emission tomography/low resolution computerized tomography (SPECT/CT) images were obtained. A total of 142 examinations were undertaken at different phases of the disease. Depreotide and gallium findings were compared visually and semi-quantitatively, with reference to the results of conventional work-up and the patients' follow-up data., Results: In most HL, intermediate- and low-grade B-cell, as well as in T-cell NHL, depreotide depicted more lesions than Ga-67 and/or exhibited higher tumor uptake. The opposite was true in aggressive B-cell NHL. However, there were notable exceptions in all lymphoma subtypes. During initial staging, 93.3% of affected lymph nodes above the diaphragm, 100% of inguinal nodes and all cases with splenic infiltration were detected by depreotide. On the basis of depreotide findings, 32% of patients with early-stage HL were upstaged. However, advanced HL and NHL cases were frequently downstaged, due to low sensitivity for abdominal lymph node (22.7%), liver (45.5%) and bone marrow involvement (36.4%). Post-therapy, depreotide detected 94.7% of cases with refractory disease or recurrence. Its overall specificity was moderate (57.1%). Rebound thymic hyperplasia, various inflammatory processes and sites of unspecific uptake were the commonest causes of false positive findings. The combination of depreotide and gallium enhanced sensitivity (100%), while various false positive results of either agent could be avoided., Conclusion: Except perhaps for early-stage HL, Tc-99m depreotide as a stand-alone imaging modality has limited value for the initial staging of lymphomas. Post-therapy, however, depreotide scintigraphy seems useful in the evaluation of certain anatomic areas, particularly in non-aggressive lymphoma types. The combination with Ga-67 potentially enhances sensitivity and specificity. If fluorodeoxyglucose positron emission tomography is not available or in case of certain indolent lymphoma types, Tc-99m depreotide may have a role as an adjunct to conventional imaging procedures.

Objective: To investigate the effect of acquisition arc (180 degrees or 360 degrees ) and attenuation correction (AC), in artifact occurrence and image uniformity of myocardial perfusion SPECT studies in normal hearts., Methods: Twenty male and 44 female patients with primary hyperparathyroidism and low probability of resting perfusion abnormalities were analysed. Tc-sestamibi myocardial perfusion studies were performed at rest with a hybrid SPECT/CT system. An anthropomorphic phantom was also imaged., Results: Without AC, a 360 degrees orbit resulted in significantly lower artifact rates compared to the standard 180 degrees in both gender groups. Differences persisted (P<0.001) even after adjusting reconstruction filter settings to compensate for disproportionate count statistics between the two arcs. However, gender-related variation was not considerably decreased and sub-diaphragmatic activity was augmented with a 360 degrees arc. After AC with either arc, substantially lower defect scores and minimal gender-related differences were obtained compared to the standard technique. A 360 degrees arc yielded lower defect rates and count variability than did the 180 degrees arc (P<0.05). These differences were small and were eliminated after weighting for dissimilar count statistics. Sub-diaphragmatic signal was amplified, particularly with 360 degrees ; severe bowel-myocardial activity overlap complicated image interpretation in 14% of cases with 360 degrees versus 8% with 180 degrees . In certain aspects, phantom imaging findings diverged from patient studies., Conclusion: Without AC there is significant disparity between 180 degrees and 360 degrees concerning artifact occurrence. After CT-based AC differences between arcs in defect rate and image uniformity seem less critical. However, 180 degrees is favoured by less intensification of intestinal activity.

Unlabelled: The purpose of the study was to compare bacterial species, clinical, laboratory and imaging findings ((99m )Tc-dimercaptosuccinic acid renal scan and voiding cystogram) in infants and children with high (>/=10(5) colony forming units (CFU)/ml, group A patients) and low (

The purposes of this study were to assess the occurrence of euthyroid sick syndrome in patients with acute myocardial infarction (AMI) or unstable angina (UA), and the relationship with beta-blocker or thrombolytic therapy. Plasma triiodothyronine (T3), reverse T3 (rT3), free T3 (FT3), thyroxine (T4), free T4 (FT4), thyroid-stimulating hormone (TSH), thyroxine-binding globulin (TBG), and albumin (ALB) levels were determined in 95 patients (59 males, 36 females, aged 58.4+/-9) with AMI and 19 patients (13 males, 6 females aged 54.7+/-12.3) with UA for 5 consecutive days from the onset of the acute syndrome and 1 month later. Patients were divided according to beta-blocker therapy and thrombolytic therapy. There was a significant T3 decrease and rT3 increase in all patients during the first 5 days following admission (p < 0.05). FT3 and FT4 remained unchanged during the study. In patients with complicated infarctions, the rT3 increase and the T3 decrease were significantly greater compared to those with uncomplicated infarctions (p<0.03). TSH, T4, TBG, and ALB were significantly (p<0.05) decreased only in complicated infarctions. No differences were observed between patients with or without thrombolysis or patients with or without beta-blocker treatment. The apparent decrease in T3, the increase in rT3 levels and the decreased TSH and T4 levels, show clearly that the euthyroid sick syndrome (low T3) occurs not only in AMI but also in UA. In addition, these hormonal changes are not affected by beta-blocker therapy and thrombolysis does not influence the occurrence of the syndrome. The degree of T3 decrease is proportional to the severity of cardiac damage and may have a possible prognostic value.

We evaluated the effectiveness of Re-186-HEDP in 25 patients with painful metastatic bone disease. Twenty-five patients with known prostatic (n = 19), non-small-cell lung cancer (n = 1) and breast cancer (n = 5) and multiple confirmed skeletal metastases were studied. All were taking analgesics daily (nonsteroidal antiinflammatory drugs/opiates). Re-186-HEDP (mean 35.2 mCi) was administered and patients were monitored for at least 50 days. In five patients, a repeat dose was administered 9 to 10 weeks later. The evaluation of the analgesic effect was based on a "pain diary" and by recording the use of analgesics. In 80% (20 of 25) of the patients, the effect was significant palliation, moderate in 3 patients (12%), and insignificant in 2 (8%). No significant myelotoxicity was observed. Transient pain flare was recorded in 8 of 25 patients. These results indicate that Re-186-HEDP can offer pain palliation in patients with painful bone metastases without being complicated by significant myelotoxicity.

The objective of the present study was to investigate the efficacy of (111)In-DTPA-octreotide (OC) for in vivo scintigraphic imaging of these relatively uncommon tumors. Thirteen patients (9 males, 4 females, mean age 59 years) with known sarcomatous lesions were studied. All patients had known lesions as demonstrated by previous investigation with other modalities, e.g. CAT, MRI. Following intravenous injection of 10 microg of OC labeled with 2.8-4.2 mCi (111)In, planar imaging was done at 6 +/- 1 and 22 +/- 2 h, respectively. Histologic verification was obtained in all cases, either from fine needle aspiration or from surgically removed tissue. Positive imaging was observed in 12/13 cases (92.3%). One scan was false-negative (7.7%). Occult lesions were demonstrated in two patients. The histologic typing and the scintigraphy results were: fibrosarcoma (1+/1), embryonic rhabdomyosarcoma (1+/1), leiomyosarcomas (3+/3), liposarcomas (2+/2), uterine sarcomas (2+/2), HIV (-) Kaposi sarcoma (1+/1), osteosarcoma (1+/1), chondrosarcoma (1-/1) and neurogenous sarcoma (1+/1). OC appears to have properties that lead to a new indication for its use. Other possible applications relate to the therapeutic use of octreotide either unlabeled or labeled with a beta-emitting radionuclide, as well as its use in radioimmunoguided surgery. Regarding the latter, our preliminary results are encouraging., (Copyright 2000 S. Karger AG, Basel)

The targeting potential of three different monoclonal antibodies (MAbs) was assessed in patients with ovarian cancer. HMFG1, OC-125 and H17E2 labelled with 111In or 123I were evaluated prospectively for their ability to localize ovarian tumour. Forty two patients with ovarian cancer, aged 40-78 years (median = 58 years) were studied using OC-125 (n = 9), HMFG1 (n = 11) and H17E2 (n = 22). Imaging data were compared with the CT and the surgical findings. Presence of tumour was confirmed in 35/42 (83%) patients (8/9 OC-125, 10/11 HMFG1 and 17/22 H17E2) and correlated well with the conventional radiology diagnostic methods. One patient with a negative H17E2 scan and a large abdominal mass detected at laparotomy revealed a PLAP-negative tumour on immunohistochemistry. Scintigraphy revealed the presence of active disease, confirmed by laparotomy/laparoscopy in 6/8 patients considered to be in clinical remission. The sensitivity of the method was high enough and the diagnostic contribution of this approach should be further evaluated.

Unlabelled: The efficacy of 99mTc-tetrofosmin for the detection of parathyroid lesions was investigated prospectively in patients with hyperparathyroidism referred for surgical treatment., Methods: Twenty-seven patients with primary and 18 with tertiary hyperparathyroidism were studied. Twelve patients had undergone one or more previous neck explorations. Static imaging with 201Tl was performed first, immediately followed by a 30-min 99mTc-tetrofosmin dynamic study. Delayed views of up to 3 hr postinjection were also obtained. Technetium-99m-pertechnetate was used for thyroid delineation. The tetrofosmin/99mTc-pertechnetate subtraction scan (TF/TC), the single-tracer washout technique and the thallium/technetium subtraction (TL/TC) were compared. Quantification of relative uptakes of tracers in the thyroid and abnormal parathyroids was accomplished by measuring activity within regions of interest. Kinetics of tetrofosmin in the thyroid and abnormal parathyroids were studied by evaluating the plots of the parathyroid to thyroid ratios against time as well as by calculation of the half-clearance times from the slow component of the time-activity curves., Results: The overall sensitivity, specificity and accuracy of TF/TC and TL/TC were 76%, 92% and 83% and 52%, 85% and 65%, respectively. The respective sensitivities were 87% and 70% for adenomas and 72% and 46% for hyperplasia. The parathyroid-to-thyroid activity ratios of tetrofosmin were significantly higher than those of thallium (p < 0.001). The tetrofosmin single-tracer washout study was less accurate than the subtraction technique (overall sensitivity and specificity, 70% and 69%, respectively). The washout properties of tetrofosmin in abnormal parathyroids were not substantially different from those in the thyroid, with a few exceptions (p = 0.4). No correlation of half-clearance times with parathyroid size, degree of early uptake, parathyroid hormone levels or histology could be established. Comparing adenomas to hyperplasia in respect to tetrofosmin retention, a statistically significant difference was observed (p = 0.005)., Conclusion: Technetium-99m-tetrofosmin is suitable for parathyroid imaging. The kinetic properties of this agent in parathyroid and thyroid tissues do not warrant differential washout protocols. The diagnostic impact of the observed difference in tetrofosmin kinetics between parathyroid adenomas and hyperplasia requires further investigation.

This preliminary nonrandomized study was conducted to evaluate the clinical usefulness of TATI and CYFRA 21-1 as tumor markers in head and neck squamous cell carcinoma. Serum levels of these markers were measured from 122 subjects of a tertiary-care university hospital, divided into four groups: (1) normal individuals and patients with (2) inflammatory pathology, (3) benign tumors and (4) squamous cell carcinoma of the head and neck. Serum samples were collected before and after treatment, with a mean follow-up period of 12 months. The cutoff level, sensitivity, specificity and likelihood ratio of a positive and negative test were: 21 microg/l, 66.6%, 93.75%, 10.6 and 0.35 for TATI; 3.3 microg/l, 28.5%, 95%, 5.7 and 0.75 for CYFRA 21-1, respectively. Both markers presented elevated mean values and statistically significant differences in the cancer patient group compared with the other groups. Significant differences were also observed between the stage of disease and tumor differentiation. TATI levels seem to relate positively to the course of disease during the follow-up period. Although CYFRA 21-1 values presented significant differences, the majority of them were under the cutoff level. We conclude that TATI seems to play a role in the clinical evaluation of head and neck squamous cell carcinoma, while the usefulness of CYFRA 21-1 is limited.

In this paper, XBONE, a hybrid medical expert system that supports diagnosis of bone diseases is presented. Diagnosis is based on various patient data and is performed in two stages. In the early stage, diagnosis is based on demographic and clinical data of the patient, whereas in the late stage it is mainly based on nuclear medicine image data. Knowledge is represented via an integrated formalism that combines production rules and the Adaline artificial neural unit. Each condition of a rule is assigned a number, called its significance factor, representing its significance in drawing the conclusion of the rule. This results in better representation, reduction of the knowledge base size and gives the system learning capabilities.

Ectopic ACTH secretion due to occult carcinoid tumours is an occasional cause of ACTH dependent Cushing's syndrome. In many cases the ectopic source may be obvious, but sometimes no obvious source is evident, the so-called occult ectopic syndrome. Due to their small size, localization of such occult tumours, particularly bronchial carcinoids, may be extremely difficult. Whole body CT and venous sampling studies have been used but are not always successful in determining the site of such lesions. We report a 40-year-old patient with the ectopic ACTH syndrome due to a 0.6-cm bronchial carcinoid tumour which was successfully localized by 111indium-DTPA labelled octreotide scintigraphy.

Purpose: Evaluate the effectiveness of fibrin glue for the embolic occlusion of needle tracks following percutaneous lung biopsy (PLB)., Methods: Twenty-six rabbits underwent computed tomography (CT)-guided PLB using a coaxial system consisting of 19- and 22-gauge needles. Thirteen rabbits were used as controls (group A). In 13 other rabbits (group B), fibrin glue labelled with I131 fibrinogen and contrast medium was injected into the track. Both groups were examined by CT for the presence and severity of pneumothorax (mild: less than 20%; severe: more than 20%). Group B was also examined scintigraphically and their lungs were studied histologically., Results: In group A, pneumothorax developed in eight animals (61.6%) and was severe in six (46.1%) whereas in group B, pneumothorax developed in five animals (38.5%) and was severe in one (7.7%). Though the difference between the two groups in overall incidence of pneumothorax was not significant (p > 0.1), it was significantly higher (p < 0.025) for severe pneumothorax in group A. No signs of systemic embolism were observed., Conclusions: Based on this animal model, fibrin glue is a safe and useful sealant following PLB and reduces the incidence of severe pneumothorax.