A phantom assessment of portable imaging and radio-guided surgery systems with technetium-99m and fluorine-18.

AIM: To perform a detailed analysis of the performance of mobile intraoperative imaging systems and gamma probes in a phantom set-up, and compare this with a conventional gamma camera. METHODS: Two separate experiments were performed. In the first, a modified Jaszczak phantom equipped with five (99m)Tc-filled hot spheres (0.5-20 ml) was analyzed using Sentinella, declipseSPECT and a conventional gamma camera under three conditions: no background, spheres on the surface of the background activity, and totally immersed spheres (contrast level in both 1: 8). In the second experiment, two phantom spheres (0.5 and 2 ml) filled with (99m)Tc and (18)F (infinite contrast, 1: 4 and 1: 8) were measured using the hand-held probes Navigator and GammaLocator DXI. Data analysis consisted of signal-to-background ratios and determination of the full-width at half-maximum (FWHM). A visual scoring was performed by three nuclear medicine physicians. RESULTS: At infinite contrast, (99m)Tc-filled spheres with volumes of at least 2 ml could be detected adequately with all systems (e.g. 2 ml sphere, FWHM: ECAM 11 mm, declipseSPECT 9 mm, Navigator 13 mm, GammaLocator 12 mm). Under decreased contrast conditions, the results for all systems were impaired and the 0.5 ml phantom sphere filled with either (99m)Tc or (18)F was only detected accurately by the GammaLocator (FWHM range: 13-17 mm). CONCLUSION: All systems are suitable for intraoperative sentinel node detection with nearly infinite signal-to-background contrast. At a lower contrast, the GammaLocator performed best for the detection of small volumes at low-contrast ratios regardless of the radionuclide.

Pathological 99mTc-sestamibi myocardial perfusion scintigraphy is independently associated with emerging cardiac events in elderly patients with known or suspected coronary artery disease.

BACKGROUND: Only few data are available regarding the prognostic impact of myocardial perfusion scintigraphy with (99m)Tc-sestamibi (MPS) regarding emerging cardiac events in elderly patients PURPOSE: To evaluate the prognostic value of MPS regarding emerging cardiac events in patients aged ≥70 years with known or suspected coronary artery disease (CAD). MATERIAL AND METHODS: One hundred and thirty-three patients (74.6 ± 3.7 years) who underwent exercise or pharmacological stress/rest MPS were included in this analysis. Semi-quantitative visual interpretation of MPS images was performed and Summed-Stress- (SSS), Summed-Difference- (SDS), and Summed-Rest Scores (SRS) were calculated. Multivariate logistic regression analyses were calculated for evaluation of the independent prognostic impact of MPS results and several cardiac-related patient characteristics with regard to emerging cardiac events. Kaplan-Meier survival- and log rank analyses were calculated for assessment of cardiac event-free survival. RESULTS: Pathological SSS (OR: 3.3), angina (OR: 2.7) and ischemic ECG (OR: 3.0) were independently associated with cardiac events. Patients with pathological SSS (p=0.005) and ischemic ECG (p=0.012) had a significantly lower incidence of cardiac event-free survival. CONCLUSION: Pathological MPS is independently associated with emerging cardiac events predicting a significantly lower incidence of cardiac event-free survival in patients aged ≥70 years.

Chronic vagus nerve stimulation for treatment-resistant depression increases regional cerebral blood flow in the dorsolateral prefrontal cortex.

The purpose of the present study was to assess the effects of vagus nerve stimulation (VNS) therapy on regional cerebral blood flow (rCBF) in depressed patients. Regional cerebral blood flow (rCBF) was assessed by [(99m)Tc]-HMPAO-single photon emission computed tomography (SPECT) before and after 10weeks of VNS in patients participating in an open, uncontrolled European multi-center study investigating efficacy and safety of VNS. Patients suffered from major depression, with a baseline score of≥20 on the 24-item Hamilton Depression Rating Scale (HDRS) and had been unsuccessfully treated with at least two adequately prescribed antidepressant drugs. Data of 15 patients could be analyzed using SPM 2. After 10weeks of VNS (20Hz, 500µs pulse width, stimulation during 30s every 5min at the maximal comfortable level) rCBF was increased in the left dorsolateral/ventrolateral prefrontal cortex (Brodmann areas 46 and 47) and decreased in the right posterior cingulate area, the lingual gyrus and the left insula. Our findings are in line with earlier results which showed that VNS increases rCBF in the left dorsolateral prefrontal cortex. The modulation of the activity in this region could be associated with the antidepressant efficacy of VNS.

Influence of 5-HTTLPR polymorphism on resting state perfusion in patients with major depression.

Neuroimaging studies in major depressive disorder (MDD) have indicated dysregulation in a network involving prefrontal cortex, subgenual cingulate and the amygdalae, which is known to be modulated by serotonin. The serotonergic system is the principal target for pharmacological treatment in MDD and the functional variable serotonin promoter polymorphism (5-HTTLPR) influences susceptibility, course and treatment response of MDD. Using data from a previously published sample of 89 MDD-patients, we examined post hoc the effect of 5-HTTLPR status on resting state perfusion, as measured with (99m)Tc-HMPAO-SPECT. MDD patients were stratified according to receptor polymorphism, both using a bi-allelic (group A: L/L vs. group B: S/S and S/L genotype) and a tri-allelic approach (Group A': LA/LA vs. Group B': non-LA/LA genotype). There were no significant differences between both subgroups regarding age, gender, severity of depression, medication, or treatment response (p > 0.1). Using the bi-allelic approach, Group B, compared to group A, revealed a significantly higher resting state perfusion in medial prefrontal cortex (p(voxel) (FWE) < 0.05). Additional ROI analyses showed relative overactivity of the amygdalae in group B (p(voxel) (FWE) < 0.05). Similar effects were observed in the tri-allelic approach. The opposite contrasts (Group A > Group B) revealed no significant effects. We demonstrate that in patients with MDD, 5-HTTLPR gene polymorphism modulates resting state perfusion in key structures of mood processing. While the clinical impact of these findings will need to be further investigated in larger cohort studies, the necessity to monitor and to account for individual 5-HTTLPR-status in future MDD imaging studies is highly recommended.

Impact of the Ki-67 proliferation index on response to peptide receptor radionuclide therapy.

PURPOSE: The role of the Ki-67 tumour proliferation index (PI) in predicting the efficacy of peptide receptor radionuclide therapy (PRRT) in gastroenteropancreatic tumours (GEP-NET) remains undetermined. This single-centre analysis focused on the potential therapeutic impact of this immunohistochemical parameter. METHODS: A total of 81 consecutive GEP-NET patients treated with (177)Lu-DOTA-octreotate (mean activity of 7.9 GBq per cycle, usually four treatment cycles at standard intervals of 3 months) were retrospectively analysed. Both an evaluable PI and tumour response (modified SWOG criteria) were required for patient inclusion. RESULTS: Response of tumours with a PI of ≤20% (partial response 40%, minor response 15%, stable disease 34%, progressive disease 11%) was comparable in all PI subsets, including those with a PI of 20%. However, G3 tumours (PI > 20%) showed progression in 71% of patients. CONCLUSION: Response to PRRT is consistent over the PI range of ≤20% (G1 + G2). Contrary to preliminary previous suggestions, a PI of 15% or 20% should not preclude candidates from somatostatin receptor-targeted radiotherapy.

The significance of 99mTc-MAA SPECT/CT liver perfusion imaging in treatment planning for 90Y-microsphere selective internal radiation treatment.

UNLABELLED: Selective internal radiation therapy (SIRT), a catheter-based liver-directed modality for treating primary and metastatic liver cancer, requires appropriate planning to maximize its therapeutic response and minimize its side effects. (99m)Tc-macroaggregated albumin (MAA) scanning should precede the therapy to detect any extrahepatic shunting to the lung or gastrointestinal tract. Our aim was to compare the ability of SPECT/CT with that of planar imaging and SPECT in the detection and localization of extrahepatic (99m)Tc-MAA accumulation and to evaluate the impact of SPECT/CT on SIRT treatment planning and its added value to angiography in this setting. METHODS: Ninety diagnostic hepatic angiograms with (99m)Tc-MAA were obtained for 76 patients with different types of cancer. All images were reviewed retrospectively for extrahepatic MAA deposition in the following order: planar, non-attenuation-corrected SPECT, and SPECT/CT. Review of angiograms and follow-up of patients with abdominal shunting served as reference standards. RESULTS: Extrahepatic accumulation was detected by planar imaging, SPECT, and SPECT/CT in 12%, 17%, and 42% of examinations, respectively. The sensitivity for detecting extrahepatic shunting with planar imaging, SPECT, and SPECT/CT was 32%, 41%, and 100%, respectively; specificity was 98%, 98%, and 93%, respectively. The respective positive predictive values were 92%, 93%, and 89%, and the respective negative predictive values were 71%, 73%, and 100%. The therapy plan was changed according to the results of planar imaging, SPECT, and SPECT/CT in 7.8%, 8.9%, and 29% of patients, respectively. CONCLUSION: In pre-SIRT planning, (99m)Tc-MAA SPECT/CT is valuable for identifying extrahepatic visceral sites at risk for postradioembolization complications.

Nucleus accumbens deep brain stimulation decreases ratings of depression and anxiety in treatment-resistant depression.

BACKGROUND: While most patients with depression respond to combinations of pharmacotherapy, psychotherapy, and electroconvulsive therapy (ECT), there are patients requiring other treatments. Deep brain stimulation (DBS) allows modulation of brain regions that are dysfunctional in depression. Since anhedonia is a feature of depression and there is evidence of dysfunction of the reward system, DBS to the nucleus accumbens (NAcc) might be promising. METHODS: Ten patients suffering from very resistant forms of depression (treatment-resistant depression [TRD]), not responding to pharmacotherapy, psychotherapy, or ECT, were implanted with bilateral DBS electrodes in the NAcc. The mean (+/-SD) length of the current episode was 10.8 (+/-7.5) years; the number of past treatment courses was 20.8 (+/-8.4); and the mean Hamilton Depression Rating Scale (HDRS) was 32.5 (+/-5.3). RESULTS: Twelve months following initiation of DBS treatment, five patients reached 50% reduction of the HDRS (responders, HDRS = 15.4 [+/-2.8]). The number of hedonic activities increased significantly. Interestingly, ratings of anxiety (Hamilton Anxiety Scale) were reduced in the whole group but more pronounced in the responders. The [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography data revealed that NAcc-DBS decreased metabolism in the subgenual cingulate and in prefrontal regions including orbital prefrontal cortex. A volume of interest analysis comparing responders and nonresponders identified metabolic decreases in the amygdala. CONCLUSIONS: We demonstrate antidepressant and antianhedonic effects of DBS to NAcc in patients suffering from TRD. In contrast to other DBS depression studies, there was also an antianxiety effect. These effects are correlated with localized metabolic changes.

Significant association of female gender with lower degree of pathological 99mTc-sestamibi scintigraphy results as well as higher cardiac-related deaths free survival in elderly patients.

BACKGROUND: The aim of the present study was to assess the impact of female gender on the extent of myocardial perfusion defects as revealed by (99m)Tc-sestamibi myocardial perfusion scintigraphy (MPS) and on emerging cardiac events (CE) in patients aged ≥ 70 years. PATIENTS AND METHODS: 86 patients aged ≥ 70 years with known or suspected CAD undergoing MPS (74.4 ± 3.2 years; women: n = 46; 53.5%) were included in this study. Semiquantitative analysis of MPS was performed and summed stress (SSS), summed difference (SDS), and summed rest scores (SRS) were calculated. Emerging CE comprised myocardial revascularization and -infarction and cardiac-related death. Multivariate regression analysis was performed to assess the independent prognostic impact of several patient related variables on MPS results. Kaplan-Meier- and log rank analyses were calculated for assessment of CE free survival as related to gender. RESULTS: Normal SSS (87.0% vs. 27.5%; p < 0.0001), SDS (80.4% vs. 27.5%; p < 0.0001), and SRS (97.8% vs. 82.5%; p = 0.023) were significantly more often found in women, whereas incidence of mildly and severely impaired SSS (6.5% vs. 35%; p = 0.001 and 2.2% vs. 25%; p = 0.002, respectively) and SDS (15.2% vs. 52.5%; p < 0.0001 and 2.2% vs. 17.5%; p = 0.023, respectively) were significantly higher in men. Multivariate logistic regression analysis revealed female gender as an independent predictor of normal SSS (odds ratio/OR: 17.6) and SDS (OR: 53.3). Female gender was associated with a significant higher cardiac-death free survival compared to male patients (p = 0.031). CONCLUSION: Female gender is independently associated with a significantly lower degree of pathological MPS results and a higher cardiac-death free survival in elderly patients.

The value of HMPAO SPECT in predicting treatment response to citalopram in patients with major depression.

Alterations of regional cerebral blood flow (rCBF) in prefrontal cortex and the anterior cingulate cortex are conspicuous imaging findings in patients with major depression (MD). While these rCBF changes have been suggested as functional disease markers, data in large patient samples examining treatment response prediction to antidepressant therapy are limited. This study examined the predictive value of Tc-99m-HMPAO-SPECT for subsequent treatment response to antidepressant therapy with citalopram in an unprecedented large collective of patients. Ninety-three patients with MD were examined with Tc-99m-HMPAO-SPECT twice, at the beginning of citalopram-treatment (T1) and after 4 weeks of treatment (T2). To determine the impact of rCBF changes associated with treatment response, the patient sample was divided into two subgroups: responders (44 patients) and non-responders (49 patients). A two-sample t-test was used to determine group-specific rCBF-differences. Age, gender and initial Hamilton Rating Scale for Depression (HRSD) were treated as regressors of no interest. The responder group revealed significant relative rCBF increases at T1 in a large region en-compassing predominantly prefrontal and temporal cortices as well as subgenual cingulate cortex. No relative rCBF decreases were detected in this group. The comparison between T1 and T2 revealed trends of rCBF decreases in inferior frontal gyrus and rCBF increases in premotor cortex in the responder group. Our data show that rCBF measurements with TC-99M-HMPAO-SPECT provide a predictor estimate for subsequent treatment response in depressed patients undergoing antidepressant therapy with citalopram. This effect is highly significant and, most notably, independent of the initial HRSD score.

Hemodynamic variables during stress testing can predict referral to early catheterization but failed to show a prognostic impact on emerging cardiac events in patients aged 70 years and older undergoing exercise (99m)Tc-sestamibi myocardial perfusion scintigraphy.

The aim of the present study was to evaluate the prognostic value of hemodynamic variables during ergometric stress testing for (99m)Tc-sestamibi myocardial perfusion scintigraphy (MPS) as compared to several patient-related variables and MPS results with regard to referral to early coronary angiography (<3 months after MPS; CA) as well as cardiac event (CE) free survival in a study population aged > or =70 years. About 90 patients aged > or =70 years (74.5 +/- 3.6 years) who underwent ergometric stress/rest MPS were included in this study. About 19 hemodynamic variables during stress testing were assessed. Semiquantitative visual interpretation of MPS images were performed and Summed-Stress-(SSS), Summed-Difference-, and Summed-Rest-Scores were calculated. Emerging CE comprised myocardial revascularization and -infarction as well as cardiac-related death. Multivariate logistic regression analyses were performed for evaluation of independent prognostic impact of hemodynamic-, MPS- and clinical-variables with regard to referral to early catheterization as well as emerging CE. Kaplan-Meier survival- and log rank analyses were calculated for assessment of CE free survival. History of CAD (Odds ratio; OR: 99.3), low rest heart rate (OR: 14.9) and low peak systolic blood pressure (OR: 15.4) during ergometric stress testing as well as pathological SSS (OR: 48.4) were significantly associated with referral to CA. History of ischemic ECG (OR: 4.7) and pathological SSS (OR: 3.7) independently predicted emerging CE and were associated with a lower CE free survival. In patients aged > or =70 years, CA is independently predicted by clinical variables, pathological results of MPS and hemodynamic variables. In contrast, hemodynamic response to stress testing failed to show any predictive impact on emerging CE.

Dose selection for radioiodine therapy of borderline hyperthyroid patients according to thyroid uptake of 99mTc-pertechnetate: applicability to unifocal thyroid autonomy?

PURPOSE: The aim of this study was to evaluate the feasibility of applying a previously described dose strategy based on (99m)Tc-pertechnetate thyroid uptake under thyrotropin suppression (TcTU(s)) to radioiodine therapy for unifocal thyroid autonomy. METHODS: A total of 425 consecutive patients (302 females, 123 males; age 63.1+/-10.3 years) with unifocal thyroid autonomy were treated at three different centres with (131)I, using Marinelli's formula for calculation of three different absorbed dose schedules: 100-300 Gy to the total thyroid volume according to the pre-treatment TcTU(s) (n=146), 300 Gy to the nodule volume (n=137) and 400 Gy to the nodule volume (n=142). RESULTS: Successful elimination of functional thyroid autonomy with either euthyroidism or hypothyroidism occurred at a mean of 12 months after radioiodine therapy in 94.5% of patients receiving 100-300 Gy to the thyroid volume, in 89.8% of patients receiving 300 Gy to the nodule volume and in 94.4% receiving 400 Gy to the nodule volume. Reduction in thyroid volume was highest for the 100-300 Gy per thyroid and 400 Gy per nodule strategies (36+/-19% and 38+/-20%, respectively) and significantly lower for the 300 Gy per nodule strategy (28+/-16%; p<0.01). CONCLUSION: A dose strategy based on the TcTU(s) can be used independently of the scintigraphic pattern of functional autonomous tissue in the thyroid.

Nasolacrimal drainage obstruction after radioiodine therapy: case report and a review of the literature.

The authors report a 54-year-old woman with papillary thyroid carcinoma (Lindsay type, pT2 N0 M1) with pulmonary metastases. After a total thyroidectomy, a series of 3 radioiodine therapies were performed with a cumulative dose of 700 mCi I-131. After termination of the therapy, the patient was initially without complaints, but approximately 6 months later, epiphora was noted, first only of the right eye and eventually of both eyes. A whole-body I-131 scan performed 1 year after final radioiodine therapy showed atypical tracer accumulation in both medial orbital regions. This finding was new compared with the scan that was done 1 year before. Dacryocystography revealed bilateral occlusion of the lacrimal drainage system. A review of the literature shows that epiphora and lacrimal duct alterations are rarely investigated and potentially underestimated side effects after high-dose radioiodine therapy.

Proteinase-3 as the major autoantigen of c-ANCA is strongly expressed in lung tissue of patients with Wegener's granulomatosis.

Proteinase-3 (PR-3) is a neutral serine proteinase present in azurophil granules of human polymorphonuclear leukocytes and serves as the major target antigen of antineutrophil cytoplasmic antibodies with a cytoplasmic staining pattern (c-ANCA) in Wegener's granulomatosis (WG). The WG disease appears as severe vasculitis in different organs (e.g. kidney, nose and lung). Little is known about the expression and distribution of PR-3 in the lung. We found that PR-3 is expressed in normal lung tissue and is upregulated in lung tissue of patients with WG. Interestingly, the parenchymal cells (pneumocytes type I and II) and macrophages, and not the neutrophils, express PR-3 most strongly and may contribute to lung damage in patients with WG via direct interaction with antineutrophil cytoplasmic antobodies (ANCA). These findings suggest that the PR-3 expression in parenchymal cells of lung tissue could be at least one missing link in the etiopathogenesis of pulmonary pathology in ANCA-associated disease.

201Tl, 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin: relative retention and clearance kinetics in retrogradely perfused guinea pig hearts.

Myocellular kinetics of 201Tl, 99mTc-MIBI, 99mTc-tetrofosmin and 99mTc-furifosmin were investigated using retrogradely-perfused guinea-pig hearts. Relative retention decreased in the order 99mTc-MIBI ==> 99mTc-tetrofosmin ==> 99mTc-furifosmin. 201Tl and 99mTc-MIBI exhibited bi- (t1,t2), 99mTc-tetrofosmin and 99mTc-furifosmin triexponential (t1,t2,t3) time-activity-curves. Latest-phase elimination-half-life increased from 201Tl (t2) ==> 99mTc-MIBI (t2) ==> 99mTc-tetrofosmin (t3) ==> 99mTc-furifosmin (t3), showing a significant increase in deteriorating myocardium for all tracers but 99mTc-furifosmin. Delayed elimination in deteriorating myocardium explains at least partly the redistribution phenomenon of 201Tl, and suggests a similar phenomenon for 99mTc-MIBI and 99mTc-tetrofosmin.