Dario Genovesi

Comparison Between Ultrafast and Standard Single-Photon Emission CT in Patients With Coronary Artery Disease: A Pilot Study

Background—A novel technology has been developed for ultrafast (UF) single-photon emission CT (SPECT) myocardial perfusion imaging by using a pinhole collimation design and multiple cadmium zinc telluride crystal arrays. The purpose of this study was to compare myocardial perfusion imaging obtained by UF-SPECT with standard (S) SPECT in patients with known or suspected coronary artery disease. Methods and Results—A total of 34 patients underwent single-day 99mTc-tetrofosmin stress/rest myocardial perfusion imaging. UF-SPECT was performed 10 minutes before S-SPECT. Images were qualitatively analyzed, and the summed stress score and summed rest score were calculated. The segmental tracer uptake value (percentage of maximum myocardial uptake) also was quantified for both UF- and S-SPECT. When only 29 of 34 patients with significant coronary lesions were analyzed, the summed stress score was 10.1±4.4 versus 6.4±2.9, respectively, for UF- and S-SPECT (P=0.002). Qualitative and quantitative per-patient analysis showed similar results in detection of coronary artery disease for UF- and S-SPECT. In contrast, per-vessel analysis demonstrated higher regional sensitivity of UF- versus S-SPECT. UF-SPECT showed higher sensitivity in detecting multivessel disease (P=0.003) versus S-SPECT. Conclusions—This pilot study confirms that UF-SPECT provides high-quality fast myocardial perfusion imaging and suggests that it may allow a more-accurate evaluation of both extent and severity of myocardial ischemia in patients with coronary artery disease.

Comparison Between Ultrafast and Standard SPECT in Patients with Coronary Artery Disease: A Pilot Study

Background—A novel technology has been developed for ultrafast (UF) single-photon emission CT (SPECT) myocardial perfusion imaging by using a pinhole collimation design and multiple cadmium zinc telluride crystal arrays. The purpose of this study was to compare myocardial perfusion imaging obtained by UF-SPECT with standard (S) SPECT in patients with known or suspected coronary artery disease. Methods and Results—A total of 34 patients underwent single-day 99mTc-tetrofosmin stress/rest myocardial perfusion imaging. UF-SPECT was performed 10 minutes before S-SPECT. Images were qualitatively analyzed, and the summed stress score and summed rest score were calculated. The segmental tracer uptake value (percentage of maximum myocardial uptake) also was quantified for both UF- and S-SPECT. When only 29 of 34 patients with significant coronary lesions were analyzed, the summed stress score was 10.1±4.4 versus 6.4±2.9, respectively, for UF- and S-SPECT (P=0.002). Qualitative and quantitative per-patient analysis showed similar results in detection of coronary artery disease for UF- and S-SPECT. In contrast, per-vessel analysis demonstrated higher regional sensitivity of UF- versus S-SPECT. UF-SPECT showed higher sensitivity in detecting multivessel disease (P=0.003) versus S-SPECT. Conclusions—This pilot study confirms that UF-SPECT provides high-quality fast myocardial perfusion imaging and suggests that it may allow a more-accurate evaluation of both extent and severity of myocardial ischemia in patients with coronary artery disease.

Assessment of myocardial adrenergic innervation with a solid-state dedicated cardiac cadmium–zinc–telluride camera: first clinical experience

AIMS To investigate the relationships between regional adrenergic innervation heterogeneity, myocardial perfusion, and contractile function obtained by means of a low-dose imaging protocol with a cadmium-zinc-telluride (CZT) dedicated camera. METHODS Twenty-eight patients with or without ischaemic heart disease underwent (123)I-metaiodobenzylguanidine (MIBG) planar scintigraphic and CZT early and delayed evaluations followed by (99m)Tc-tetrofosmin rest gated CZT with a single-day protocol. The heart-to-mediastinum ratio and the washout rate were computed from planar (123)I-MIBG images. The summed (123)I-MIBG defect scores (SS-MIBG) were semi-quantitatively assessed from CZT images. The summed rest score (SRS), summed motion score (SMS), and summed thickening score (STS) were quantitated from (99m)Tc-tetrofosmin images. RESULTS Sixteen patients showed a depressed left ventricular systolic function [ejection fraction (EF)<50%]. They presented higher SRS (P = 0.007), SMS (P < 0.001), STS (P < 0.001), and early SS-MIBG (P = 0.007) values than those with normal contractile function. Interestingly, higher early SS-MIBG values, index of regional sympathetic innervation heterogeneity, clustered with more elevated SRS (P = 0.023), and more impaired measures of regional and global left ventricle systolic function, i.e. SMS (P = 0.046), STS (P = 0.014), and EF (P = 0.027). At multivariate analysis, a higher SRS (P = 0.039) remained the only independent predictor of more elevated early SS-MIBG values. In the 20 of 28 ischaemic patients, the correlations between early SS-MIBG and SMS (P = 0.017) and also STS (P = 0.036) were further confirmed. The effective dose of the investigation was 4.2 ± 0.72 mSv. CONCLUSIONS An altered early SS-MIBG, assessed with a low-dose imaging protocol and a CZT cardiac camera, identifies patients with more impaired myocardial perfusion and contractile function.

Dynamic 3D Analysis of Myocardial Sympathetic Innervation: An Experimental Study Using 123I-MIBG and a CZT Camera

Data on the in vivo myocardial kinetics of 123I-metaiodobenzylguanidine (123I-MIBG) are scarce and have always been obtained using planar acquisitions. To clarify the normal kinetics of 123I-MIBG in vivo over time, we designed an experimental protocol using a 3-dimensional (3D) dynamic approach with a cadmium zinc telluride (CZT) camera. Methods: We studied 6 anesthetized pigs (mean body weight, 37 ± 4 kg). Left ventricular myocardial perfusion and sympathetic innervation were assessed using 99mTc-tetrofosmin (26 ± 6 MBq), 123I-MIBG (54 ± 14 MBq), and a CZT camera. A normal perfusion/function match on gated SPECT was the inclusion criterion. A dynamic acquisition in list mode started simultaneously with the bolus injection of 123I-MIBG, and data were collected every 5 min for the first 20 min and then at acquisition steps of 30, 60, 90, and 120 min. Each step was reconstructed using dedicate software and reframed (60 s/frame). On the reconstructed transaxial slice that best showed the left ventricular cavity, regions of interest were drawn to obtain myocardial and blood pool activities. Myocardial time–activity curves were generated by interpolating data between contiguous acquisition steps, corrected for radiotracer decay and injected dose, and fitted to a bicompartmental model. Time to myocardial maximum signal intensity (MSI), MSI value, radiotracer retention index (RI, myocardial activity/blood pool integral), and washout rate were calculated. The mediastinal signal was measured and fitted to a linear model. Results: The myocardial MSI of 123I-MIBG was reached within 5.57 ± 4.23 min (range, 2–12 min). The mean MSI was 0.426% ± 0.092%. Myocardial RI decreased over time and reached point zero at 176 ± 31 min (range, 140–229 min). The ratio between myocardial and mediastinal signal at 15 and 125 min and extrapolated at 176 and 4 h was 5.45% ± 0.61%, 4.33% ± 1.23% (not statistically significant vs. 15 min), 3.95% ± 1.46% (P < 0.03 vs. 125 min), and 3.63% ± 1.64% (P < 0.03 vs. 176 min), respectively. Mean global washout rate at 125 min was 15% ± 14% (range, 0%–34%), and extrapolated data at 176 min and 4 h were 18% ± 18% (range, 0.49%–45%) and 25% ± 23% (range, 1.7%–56.2%; not statistically significant vs. 176 min), respectively. Conclusion: 3D dynamic analysis of 123I-MIBG suggests that myocardial peak uptake is reached more quickly than previously described. Myocardial RI decreases over time and, on average, is null about 3 h after injection. The combination of an early peak and variations in delayed myocardial uptake could result in a wide physiologic range of washout rates. Mediastinal activity appears to be constant over time and significantly lower than previously described in planar studies, resulting in a higher heart-to-mediastinum ratio.

Accuracy of 99mTc-Hydroxymethylene diphosphonate scintigraphy for diagnosis of transthyretin cardiac amyloidosis.

Background and AimEither 99mTechnetium diphosphonate (Tc-DPD) or pyrophosphate (Tc-PYP) scintigraphy plays a relevant role in diagnosing transthyretin cardiac amyloidosis (CA), and labeled radiotracers have been extensively studied in diagnosing CA. Few studies have analyzed and validated 99mTc-Hydroxymethylene diphosphonate (Tc-HMDP). Our aim was to validate the diagnostic accuracy of Tc-HMDP total-body scintigraphy in a cohort of patients with biopsy-proven transthyretin CA.Methods and ResultsWe retrospectively evaluated all patients undergoing 99mTc-HMDP total-body scintigraphy, in adjunct to a comprehensive diagnostic work-up for suspected CA. Sixty-five patients were finally diagnosed with CA, while it was excluded in 20 subjects with left ventricular hypertrophy of various etiologies. Twenty-six patients had AL-CA, 39 had TTR CA (16 TTRm, 23 TTRwt). At Tc-HMDP scintigraphy, 2 AL patients showed a Perugini score grade 1 heart uptake, while 24 showed no uptake. All TTR patients showed Tc-HMDP uptake, with three patients showing a Perugini score grade 1, 16 grade 2, and 20 grade 3, respectively. No uptake was observed in patients with left ventricular hypertrophy. A positive Tc-HMDP scintigraphy showed a 100% sensitivity and a 96% specificity for TTR CA identification.ConclusionsTc-HMDP scintigraphy is as accurate as Tc-DPD or Tc-PYP, and may therefore de facto be considered a valuable tool for the diagnosis of TTR CA.

Evaluation of a method for activity estimation in Sm-153 EDTMP imaging.

Absolute activity evaluation is fundamental for internal radionuclide dosimetry when patient-specific therapy optimization is wanted. Often, quantification is attempted with 3D SPECT image based (IB) methods, but the true concentration values can be underestimated due to the partial volume effect (PVE). This is especially true when small diffuse lesions are present. In this paper, we describe a 3D region of interest (ROI) based quantification method (LS-ROI), which estimates the ROI concentration values directly from the projection data acquired in the tomographic scan once ROIs have been segmented on a CT and/or a SPECT image. The method, which has inherent PVE correction capabilities, was applied both on simulated and on real phantom data. Simulations reflected the case of a patient with bone metastases treated with 153Sm-EDTMP: Both the activity in the metastases and the total retention in the skeleton were evaluated. Thirty noisy data sets were produced in order to evaluate the accuracy and precision of the method. The effect of region segmentation errors on estimated concentrations was thoroughly investigated. Real data were acquired on a NEMA phantom, where a cylindrical central region (283 cm3) simulated the bone and two spheres (10.3 and 25.5 cm3) simulated the metastases. The results obtained with the LS-ROI method were compared with those of a conventional 3D IB method and those of a quantitative conjugate view approach derived from LS-ROI and applied to the anterior and posterior views acquired in the tomographic scan (LS-ROI anterior-posterior: LS-ROI-AP). Simulations showed that when the geometry of regions is known, the LS-ROI method recovered the simulated concentration values within 20%, while the IB method underestimated the concentration in high activity small lesions by as much as 49%. Segmentation errors, up to 44% of the true region volume, produced a higher variation in LS-ROI estimates than in IB ones; however, the overall bias of the LS-ROI estimates (< or = 25%) remained lower than that of IB estimates. In the case of the evaluation of the total retention in the skeleton, the LS-ROI method recovered the simulated value within 2%, while IB underestimated it up to 13%. In all the cases, the LS-ROI-AP method showed an accuracy comparable with that of the LS-ROI one, and a worse precision just because of the lower number of counts used in the analysis. However, a worsening of LS-ROI-AP performances was demonstrated in the case of strong overlap of regions: In this case, a bias of up to 40% was observed. The results obtained on real phantom data confirmed the simulation results: The IB method underestimated activity up to 47% in the smallest sphere, while the bias was reduced to 13% with LS-ROI and LS-ROI-AP estimates. The good quantification capabilities of the LS-ROI method can be useful for absolute activity quantification in the case of small active diffused lesions and constitute the basis for the development of an accurate patient-specific planning strategy in internal radionuclide treatments, provided there is a reliable segmentation of lesions.

PET-CT evaluation of amyloid systemic involvement with [18F]-florbetaben in patient with proved cardiac amyloidosis: a case report

BackgroundOne of the most frequent disorders which lead to cardiac amyloidosis is transthyretin-related amyloidosis (ATTR). Some PET radio-pharmaceuticals for the detection of beta-amyloid deposits within the brain have shown to be able to detect also cardiac amyloid deposits. We present a case of a man with ATTR studied with [18F]-florbetaben PET-CT.ResultsTotal-body scan showed a moderate uptake in the bone marrow, especially in correspondence of the vertebral column, while no significant myocardial uptake was present. Cardiac-focused scans showed low mean cardiac SUV values confirming the absence of significant myocardial uptake. Brain scan showed a significant cortical brain uptake of the radio-pharmaceutical more evident in correspondence of frontal and temporal lobes.ConclusionsDistinct subtypes of amyloidosis show different uptake of the radiotracer. Brain amyloid deposition in the presence of a systemic disease could not be caused by the same amyloid precursor.

Striatal Dopamine Transporter Modulation After Rotigotine: Results From a Pilot Single-Photon Emission Computed Tomography Study in a Group of Early Stage Parkinson Disease Patients

Introduction Several in vitro data have reported negative interference by dopamine-agonists on the expression of dopamine transporter (DAT), whereas the majority of imaging studies have shown that neither L-dopa nor dopamine-agonists interfere with DAT availability. As yet, there are no in vivo studies on DAT expression after treatment with rotigotine. Methods We evaluated presynaptic nigrostriatal function in 8 patients with de novo Parkinson disease (age, 59 ± 6.2 years; male/female sex, 5/3) using 123-I- N-&ohgr;-fluoropropyl-2-&bgr;-carbomethoxy-3-&bgr;-(4-iodophenyl)nortropane (FP-CIT) single-photon emission computed tomography before and after 3 months of treatment with rotigotine (mean dose, 7.75 ± 1.98 mg). For data analysis, specific (left and right caudate, left and right putamen) to nonspecific (occipital cortex) binding ratios, putamen-to-caudate ratios, and asymmetry indices were calculated. Results After rotigotine, motor symptoms improved in all patients (Unified Parkinson Disease Rating Scale III mean score, 11.88 ± 2.59 vs 7.63 ± 1.92 on therapy; P = 0.0022). Striatal FP-CIT levels showed a significant improvement in every patient at the follow-up scan. Comparisons between before and after treatment in the whole group revealed a significant improvement in FP-CIT uptake in both caudate and putamen (P < 0.001 in each nucleus). Putamen-to-caudate ratio and asymmetry indices did not show any significant difference before and after treatment. Discussion Although the study population was small, we found DAT overexpression after chronic treatment with rotigotine, presumably related to its pharmacological profile. The DAT upregulation by rotigotine in an opposite direction with respect to early Parkinson disease compensatory mechanisms might reduce the risk of dyskinesia, but it could imply less motor benefit because of less stimulation by the dopamine itself on dopaminergic receptors.

Prognostic Significance of 2-Deoxy-2-[18F]-Fluoro-D-Glucose PET/CT in Patients With Locally Advanced Esophageal Cancer Undergoing Neoadjuvant Chemoradiotherapy Before Surgery: A Nonparametric Approach.

AbstractTo investigate the prognostic value of tumor metabolism measurements on serial 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography and computed tomography scans in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiotherapy.Forty-five patients (63 ± 7 years, 6 female) treated with concomitant chemoradiotherapy before surgery were followed up for 24 ± 18 months (range 4–71). Positron emission tomography and computed tomography scans were obtained within 1 week before the start (PET1) and 1 month after the completion of the treatment (PET2). Total body tumor metabolic activity was measured as the sum of the parameters: SUVmax, SUV corrected for lean body mass, and total lesion glycolysis (TLG40/50/70%). Then, delta values for the parameters between PET1 and PET2 were calculated and expressed as percentage of PET1 results.At the time of the analysis, 27 patients were dead and 18 were alive. There was no difference between the 2 groups in terms of age, sex, site of the disease, histology, and the presence/absence of linfonodal metastases (P = NS). Survival random forest analysis (20,000 trees) resulted in an estimate of error rate of 36%. The nonparametric approach identified &Dgr;TLG40 as the most predictive factor of survival (relative importance 100%). Moreover, T (17%), N (5%), and M (5%) stage of the disease, cancer histology (11%), TLG70 (5%) at the end of chemioradioterapy, and &Dgr;TLG50–70 (17%–5%) were positively associated with patient outcome.The nonparametric analysis confirmed the prognostic importance of some clinical parameters, such as TNM stage and cancer histology. Moreover, &Dgr;TLG resulted to be the most important factor in predicting outcome and should be considered in risk stratification of patients treated with neoadjuvant chemoradiotherapy.

Nuclear cardiology at the door of a new era: better to save mSv or to reduce imaging time?

#Nuclear cardiology in the last 30 years The evolution of nuclear cardiology has gone through several clinical protocols that can be summarized as 201 Tl stress/redistribution, 201 Tl stress/redistribution with delayed imaging, 201 Tl stress/redistribution with reinjection, singleor double-day 99m Tc-labelled radiotracers, and 201 Tl/ 99m Tc combined approaches. This evolution covered more or less 30 years with a significant (at least 25 %) increase in the accuracy of the method, but (up to few years ago) a decrease in the mSv to the patient of less than 5 %. Recent advances in hardware and software applied to nuclear cardiology [1] have led to short imaging times and/or low-dose studies, but the choice of the best combination is still difficult.