The impact of transmission-emission misregistration on the interpretation of SPET/CT myocardial perfusion studies and the value of misregistration correction.

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.

Assessment of absolute Tc-99m tetrofosmin retention in the myocardium as an index of myocardial blood flow and coronary flow reserve by gated-SPECT/CT: a feasibility study.

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.

Tc-99m depreotide SPECT/CT for lymph node staging of non-small-cell lung cancer.

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.

CT-based attenuation correction in Tl-201 myocardial perfusion scintigraphy is less effective than non-corrected SPECT for risk stratification.

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.

(99m)Tc sestamibi as a prognostic factor of response to first-line therapy and outcome in patients with malignant lymphoma.

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.

ST-segment depression during vasodilator stress is of minor clinical importance in women with normal myocardial perfusion imaging and low or intermediate risk of coronary artery disease.

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.

Technetium-99m depreotide imaging by single photon emission tomography/low resolution computed tomography in malignant lymphomas: comparison with gallium-67 citrate.

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.

Comparison between 180 degrees and 360 degrees acquisition arcs with and without correction by CT-based attenuation maps in normal hearts at rest.

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.