Gianmauro Sacchetti

Spatial and Temporal Heterogeneity of Regional Myocardial Uptake in Patients Without Heart Disease Under Fasting Conditions on Repeated Whole-Body 18F-FDG PET/CT

Imaging of cardiac 18F-FDG uptake is used in the diagnostic evaluation of residual viable myocardium. Although, originally, hibernating myocardium was identified by a mismatch between perfusion defect and relatively preserved 18F-FDG uptake, at present several studies propose that 18F-FDG distribution can also be used alone for this purpose. Nevertheless, even severe myocardial 18F-FDG uptake defects are frequently observed in cancer patients without any cardiac disease. The aim of this study was to retrospectively analyze global and regional 18F-FDG cardiac images of 49 consecutive cancer patients free of cardiac diseases who submitted to 3 PET scans under fasting conditions. Methods: Images were acquired with a high-resolution PET/CT scanner. Three-dimensional regions of interest were drawn on the fused PET/CT images to measure the maximal standardized uptake value of the left ventricular myocardium (SUVMyo) as well as the average SUV of the left ventricular blood (SUVLV) and of the liver (SUVLiver). Analysis of regional myocardial 18F-FDG uptake was performed on a subsample of 26 patients by an automatic recognition of endocardial and epicardial borders and subdividing the left ventricle in 20 segments. Regional 18F-FDG distribution was defined as the percentage of SUVMyo in each region. Results: SUVMyo as well as SUVLV and SUVLiver did not change on average throughout the studies. This stability was not caused by a persistent pattern of myocardial 18-FDG distribution. Rather, it was associated with important variations in both directions over time. Regional 18F-FDG distribution was largely heterogeneous in all 3 studies, with a variation coefficient in each patient of 18% ± 7%, 18% ± 5%, and 17% ± 5%, respectively. An 18F-FDG uptake of <50% occurred in 78, 102, and 69 of 468 segments, although it disappeared in 55% of instances at subsequent examinations. Regional temporal variability was also marked: The absolute value of the difference in percent uptake was 10.1% ± 7.3% from test 1 to test 2, 8.0% ± 7.0% from test 1 to test 3, and 9.2% ± 6.9% from test 2 to test 3. Overall from one test to another, uptake increased or decreased by >10% in 76 and in 116 of 468 segments, respectively. Conclusion: The large spatial and temporal heterogeneity of the myocardial metabolic pattern, in cancer patients free of any disease, suggests a word of caution on the use of 18F-FDG alone as a diagnostic tool for myocardial viability.

FDG-PET/CT imaging for staging and target volume delineation in conformal radiotherapy of anal carcinoma

BackgroundFDG-PET/CT imaging has an emerging role in staging and treatment planning of various tumor locations and a number of literature studies show that also the carcinoma of the anal canal may benefit from this diagnostic approach. We analyzed the potential impact of FDG-PET/CT in stage definition and target volume delineation of patients affected by carcinoma of the anal canal and candidates for curative radiotherapy.MethodsTwenty seven patients with biopsy proven anal carcinoma were enrolled. Pathology was squamous cell carcinoma in 20 cases, cloacogenic carcinoma in 3, adenocarcinoma in 2, and basal cell carcinoma in 2. Simulation was performed by PET/CT imaging with patient in treatment position. Gross Tumor Volume (GTV) and Clinical Target Volume (CTV) were drawn on CT and on PET/CT fused images. PET-GTV and PET-CTV were respectively compared to CT-GTV and CT-CTV by Wilcoxon rank test for paired data.ResultsPET/CT fused images led to change the stage in 5/27 cases (18.5%): 3 cases from N0 to N2 and 2 from M0 to M1 leading to change the treatment intent from curative to palliative in a case.Based on PET/CT imaging, GTV and CTV contours changed in 15/27 (55.6%) and in 10/27 cases (37.0%) respectively. PET-GTV and PET-CTV resulted significantly smaller than CT-GTV (p = 1.2 × 10-4) and CT-CTV (p = 2.9 × 10-4). PET/CT-GTV and PET/CT-CTV, that were used for clinical purposes, were significantly greater than CT-GTV (p = 6 × 10-5) and CT-CTV (p = 6 × 10-5).ConclusionsFDG-PET/CT has a potential relevant impact in staging and target volume delineation of the carcinoma of the anal canal. Clinical stage variation occurred in 18.5% of cases with change of treatment intent in 3.7%. The GTV and the CTV changed in shape and in size based on PET/CT imaging.

Whole-body diffusion-weighted magnetic resonance imaging in the staging of oncological patients: comparison with positron emission tomography computed tomography (PET-CT) in a pilot study

PurposeThe aim of this pilot study was to compare positron emission tomography computed tomography (PET-CT) and whole-body DWIBS in staging oncological patients to determine the staging accuracy of whole-body DWIBS.Materials and methodsWe initiated a prospective, blinded investigation on 29 patients affected by oncological diseases (n=14) or lymphoma (n=15), who underwent fluorodeoxyglucose (FDG)-based PET-CT and whole-body DWIBS for restaging purposes. Magnetic resonance (MR) imaging was conducted with a multistack (n=4) DWIBS pulse sequence. Images were read independently by two experienced radiologists and one nuclear physician. Statistical analysis assessed interobserver agreement and diagnostic accuracy.ResultsWhole-body DWIBS had a room occupation time of 20 min. Mean postprocessing time was 15 min (range 10–17 min). Mean reading time was 20 min for reader 1 (range 15–25 min) and 18 min for reader 2 (range 13–22 min). Interobserver agreement was almost perfect (=0.93). Reader 1 had a sensitivity of 89.07%, a specificity of 98.5%, and an accuracy of 97.65%, with a positive predictive value (PPV) of 85.48% and a negative predictive value (NPV) of 98.91%. Reader 2 had a sensitivity of 87.39%, a specificity of 98.39% and a diagnostic accuracy of 97.8%, with a PPV of 88.13% and a NPV of 98.75%.ConclusionsThe whole-body DWIBS protocol provided a fast whole-body examination with high specificity and NPV. One major bias of the study was the inclusion of patients with diffuse disease and advanced disease stage and the heterogeneity of the neoplastic diseases included.RiassuntoObiettivoLo scopo dello studio è il confronto tra la risonanza magnetica con difflusione total-body (WBDWIBS) e la TAC-PET nella stadiazione dei pazienti oncologici al fine di valutarne l’accuratezza diagnostica.Materiali e metodiAbbiamo avviato uno studio prospettico, in cieco, su 29 pazienti oncologici (15 con linfoma e 14 con altre neoplasie), che si sono sottoposte nel loro normale percorso diagnostico a TAC-PET con fluro-desossi-glucosio (FDG) e anche ad un’indagine con WB-DWIBS, per restaging di malattia. L’esame RM è stato condotto con una sequenza DWIBS acquisita in multipli pacchetti (4). Le immagini sono state lette indipendentemente da due radiologi esperti e un medico nucleare non consapevoli del quadro clinico dei pazienti. Sono stati calcolati la concordanza inter-osservatore e l’accuratezza diagnostica.RisultatiIl protocollo WB-DWIBS ha occupato la macchina per un totale di 20 minuti. Il tempo medio di post-elaborazione è stato di 15 minuti (10–17). Il tempo di lettura medio è stato di 20 minuti per il lettore 1 (15–25) e 18 minuti per il lettore 2 (13–22). L’agreement tra i due radiologi è risultata quasi perfetta (κ=0,93). Rispettivamente i due radiologi hanno avuto una sensibilità del 89,07% e 87,39%, specificità del 98,5% e del 98,39%, accuratezza diagnostica del 97,65% e 97,8% per i due lettori, PPV del 85,48% e 88,13% e NPV 98,91 e 98,75%.ConclusioniIl protocollo WB-DWIBS è risultato un esame total-body veloce, con elevata specificità e NPV. Un difetto dello studio è sicuramente l’arruolamento di pazienti con lesioni multiple disseminate, l’eterogeneità della casistica.

Delineation of target volume for radiotherapy of high-grade gliomas by 99m Tc-MIBI SPECT and MRI fusion.

Background and Purpose:Computed tomography (CT) and magnetic resonance imaging (MRI) are traditionally used for treatment planning of high-grade glioma. 99mTc-methoxy-isobutyl-isonitrile (MIBI) single-photon emission computed tomography (SPECT) showed high sensitivity and specificity in literature series. In the present study, it was investigated how the information provided by 99mTc-MIBI SPECT and MRI fusion could affect target delineation for radiotherapy of high-grade glioma.Patients and Methods:21 patients with high-grade glioma were studied by MRI and 99mTc-MIBI SPECT imaging. The gross tumor volume (GTV) was outlined on MRI (MRI-GTV) and SPECT images (SPECT-GTV). Three additional volumes were analyzed: the (MRI+SPECT)-GTV representing the whole amount of MRI-GTV plus SPECT-GTV, the (MRI&SPECT)-GTV identified by the overlapping region of MRI-GTV and SPECT-GTV, and the (SPECT/MRI)-GTV identified by the extension of SPECT-GTV outside MRI-GTV.Results:MRI contrast-enhanced and 99mTc-MIBI SPECT-positive lesions were found in all 21 patients. The average SPECT-GTV was slightly larger than the average MRI-GTV, with greater difference for resected than for unresected cases. The average increment of (MRI+SPECT)-GTV compared to MRI-GTV was 33%, being significantly higher for resected than for unresected cases (p = 0.006).Conclusion:The fusion of 99mTc-MIBI SPECT and MRI significantly affected the delineation of the target volume identified by MRI alone.Hintergrund und Ziel:Computertomographie (CT) und Magnetresonanztomographie (MRT) werden üblicherweise für die Bestrahlungsplanung maligner Gliome verwendet. Die Single-Photon-Emissionscomputertomographie (SPECT) mit 99mTc-Methoxy-Isobutyl-Isonitril (MIBI) zeigte in Literaturserien eine hohe Sensitivität und Spezifität. In der vorliegenden Studie wurde untersucht, wie die durch 99mTc-MIBI-SPECT- und MRT-Bildfusion bereitgestellten Informationen die Zielvolumendefinition maligner Gliome beeinflussen können.Patienten und Methodik:21 Patienten mit malignen Gliomen wurden mit MRT und 99mTc-MIBI-SPECT untersucht. Das makroskopische Tumorvolumen („gross tumor volume“ [GTV]) wurde auf MRT-(MRT-GTV) und SPECT-Bildern (SPECT-GTV) umrissen. Drei zusätzliche Volumen wurden analysiert: (MRT+SPECT)-GTV, d.h. die Summe von MRT-GTV und SPECT-GTV, (MRT&SPECT)-GTV, d.h. der sich überlappende Bereich von MRT-GTV und SPECT-GTV, und (SPECT/MRT)-GTV, d.h. die Ausbreitung des SPECT-GTV außerhalb des MRT-GTV.Ergebnisse:MRT-kontrastverstärkte und 99mTc-MIBI-SPECT-positive Läsionen wurden bei allen 21 Patienten gefunden. Das durchschnittliche SPECT-GTV war etwas größer als das durchschnittliche MRT-GTV, wobei sich ein größerer Unterschied für operierte als für nicht operierte Patienten fand. Die durchschnittliche Zunahme des (MRT+SPECT)-GTV betrug im Vergleich zum MRT-GTV 33% und war bei operierten Patienten signifikant größer als bei nicht operierten Patienten (p = 0,006).Schlussfolgerung:Die Bildfusion von 99mTc-MIBI-SPECT und MRT hatte erheblichen Einfluss auf die durch alleinige MRT bestimmte Zielvolumendefinition, insbesondere bei operierten Patienten.

The effect of activity outside the field of view on image quality for a 3D LSO-based whole body PET/CT scanner

The purpose of this study was to quantify the influence of outside field of view (FOV) activity concentration (A(c)(,out)) on the noise equivalent count rate (NECR), scatter fraction (SF) and image quality of a 3D LSO whole-body PET/CT scanner. The contrast-to-noise ratio (CNR) was the figure of merit used to characterize the image quality of PET scans. A modified International Electrotechnical Commission (IEC) phantom was used to obtain SF and counting rates similar to those found in average patients. A scatter phantom was positioned at the end of the modified IEC phantom to simulate an activity that extends beyond the scanner. The modified IEC phantom was filled with (18)F (11 kBq mL(-1)) and the spherical targets, with internal diameter (ID) ranging from 10 to 37 mm, had a target-to-background ratio of 10. PET images were acquired with background activity concentrations into the FOV (A(c)(,bkg)) about 11, 9.2, 6.6, 5.2 and 3.5 kBq mL(-1). The emission scan duration (ESD) was set to 1, 2, 3 and 4 min. The tube inside the scatter phantom was filled with activities to provide A(c)(,out) in the whole scatter phantom of zero, half, unity, twofold and fourfold the one of the modified IEC phantom. Plots of CNR versus the various parameters are provided. Multiple linear regression was employed to study the effects of A(c)(,out) on CNR, adjusted for the presence of variables (sphere ID, A(c)(,bkg) and ESD) related to CNR. The presence of outside FOV activity at the same concentration as the one inside the FOV reduces peak NECR of 30%. The increase in SF is marginal (1.2%). CNR diminishes significantly with increasing outside FOV activity, in the range explored. ESD and A(c)(,out) have a similar weight in accounting for CNR variance. Thus, an experimental law that adjusts the scan duration to the outside FOV activity can be devised. Recovery of CNR loss due to an elevated A(c)(,out) activity seems feasible by modulating the ESD in individual bed positions according to A(c)(,out).

Detection of moderate and severe coronary artery stenosis with technetium-99m tetrofosmin myocardial single-photon emission tomography

Abstract.The aim of this study was to determine the diagnostic accuracy of technetium-99m tetrofosmin myocardial imaging for the localization of coronary artery stenoses of different degrees of severity. Stress-rest single-photon emission tomography (SPET) was performed on separate days in 80 patients (64 males, 16 females; mean age 61 years; 43 patients with previous myocardial infarction; 18 patients with pharmacological stress), within 6 months of coronary angiography. Scintigraphic images were blindly and independently evaluated by three observers. Coronary stenosis was defined as a >50% narrowing in luminal diameter; severe stenosis was defined as a proximal stenosis of >75% or a peripheral stenosis of >90%. Coronary angiography revealed normal coronary arteries or insignificant coronary stenosis in 13 patients and significant coronary stenoses in 67 patients. The sensitivity and specificity of 99mTc-tetrofosmin SPET in respect of severely stenosed vessels were, respectively, 80% and 65% for the left anterior descending artery (LAD), 100% and 46% for the right coronary artery (RCA) and 58 and 78% for the left circumflex artery (LCx) territories. Considering all the significantly stenosed vessels, a significant decrease in sensitivity was observed for LAD territories (to 59%, P=0.05), and a nonsignificant decrease for RCA (88%) and LCx (47%) territories while specificity values remained essentially unchanged. No significant changes in sensitivity or specificity were observed when regions with previous myocardial infarction were excluded. In conclusion, the sensitivity of 99mTc-tetrofosmin SPET for the localization of individual stenosed vessels is only moderate when all significant stenoses are considered, but the ability of this technique to predict the location of severe coronary artery stenoses seems satisfactory, with the exception of the low specificity in respect of RCA territories.

Does baseline [18F] FDG-PET/CT correlate with tumor staging, response after neoadjuvant chemoradiotherapy, and prognosis in patients with rectal cancer?

Background[18F] fluorodeoxyglucose positron emission tomography/computed tomography ([18F] FDG-PET/CT) may be used for tumor staging and prognosis in several tumors but its role in rectal cancer is still debated. The aim of the present study was to assess the correlation of baseline [18F] FDG-PET parameters with tumor staging, tumor response (tumor regression grade (TRG)), and outcome in a series of patients affected by locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (CRT).MethodsOne hundred patients treated with neoadjuvant CRT and radical surgery were enrolled in the present study. Maximum standardized uptake value (SUVmax), SUVmean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) at the baseline [18F] FDG-PET were calculated. These PET parameters were correlated with tumor staging, histopathological data (TRG1 vs. TRG2–5 and TRG1–2 vs. TRG3–5), disease-free survival, and overall survival.ResultsSUVmax and SUVmean of primary tumor were statistically associated with T4-stage. SUVmax, SUVmean, and TLG did not result statistically associated with TRG (TRG1 or TRG1–2). MTV resulted statistically associated with TRG1–2 group (OR 2.9; 95% CI 1.2–7.1). Finally, no PET parameter was significantly associated with disease-free or overall survival.ConclusionOur results showed that baseline [18F] FDG-PET parameters correlated with tumor staging, and only MTV correlated with TRG 1–2. PET parameters failed to predict disease-free and overall survival after treatment completion. The results leave open to further studies the issue of identifying patients suitable for conservative approaches.

Reply: High Intraindividual Variability of Global Myocardial 18F-FDG Uptake over Time

TO THE EDITOR: Recently, Inglese et al. documented an extreme variability in the spatial and temporal heterogeneity of regional myocardial uptake on repeated whole-body 18F-FDG PET/CT in fasting oncologic patients without heart disease (1). The authors cautiously attributed uptake defects on myocardial 18F-FDG imaging to scar tissue, unless the defects are associated with severe hypoperfusion on 18F-FDG imaging used alone to evaluate myocardial viability. Furthermore, there are suggestions that 18F-FDG PET can detect radiation-induced myocardial damage early (e.g., in patients with esophageal cancer), but high myocardial 18F-FDG uptake corresponded to irradiated fields in only 20% of patients (2). In a case report, 18F-FDG PET/CT demonstrated an excellent concordance between increased myocardial 18F-FDG uptake and irradiated fields (3). On the other hand, physiologic myocardial 18F-FDG uptake in fasting individuals free of any heart disease is controversial. Khandani et al. reported that a subjective visual determination of cardiac 18F-FDG uptake did not change significantly over time in 47 oncologic patients who underwent 4 to 9 serial PET scans (4). In contrast, de Groot et al. found that visual grading of myocardial 18F-FDG uptake changed significantly in nearly two thirds of 25 oncologic patients who underwent at least 3 serial PET scans (5). We would like to report a 29-y-old man without evidence or a history of heart disease who showed an extremely high variability of global myocardial 18F-FDG uptake on 3 PET/CT scans. The patient was diagnosed with rhabdomyosarcoma of the right testis and underwent ablative surgery but still had multiple pulmonary and several lymphogenic metastases. The first 18F-FDG PET/CT scan was performed in October 2007 after 4 cycles of palliative chemotherapy and showed metastatic disease in the right and left lungs and inguinal lymph node involvement, but myocardial 18FFDG uptake (maximal standardized uptake value [SUVmax], 2.7; mean [6SD] standardized uptake value [SUVmean], 1.6 6 0.2) was comparable to the mediastinal background level. A second scan in January 2008 showed partial metabolic remission of these lung metastases after high-dose chemotherapy with carboplatin and etoposide followed by autologous stem cell transplantation in November 2007 but high global myocardial 18F-FDG uptake (SUVmax, 7.1; SUVmean, 4.5 6 0.8). The patient had never received radiation treatment. Therefore, we did not observe radiation-related myocardial damage in the second PET/CT scan. Seven weeks later, in February 2008, the patient underwent the third PET/CT scan, which was performed because of suspected progressive disease under ongoing chemotherapy for consolidation but found metabolically (and morphologically) stable disease. The image showed myocardial 18F-FDG uptake comparable to the mediastinal background level of the first scan (SUVmax, 2.5; SUVmean, 1.5 6 0.2). All routinely measured external parameters during the 3 scans were almost identical. The patient fasted at least 12 h before each examination. The blood glucose levels at the times of the first, second, and third scans were 6.0, 4.7, and 5.2 mmol/L, respectively, and the levels of creatinine (58 mmol/L at scan 1 and 54 mmol/L at scan 3) and TSH (1.85 mIU/L at scan 1 and 1.91 mIU/L at scan 3) were always within the reference range. The administered activities were 332, 313, and 317 MBq of 18F-FDG, and the scans started at 1 h 4 min, 59 min, and 59 min after injection. Of course, the reconstruction parameters for all images were identical. A 300% (!) increase in global myocardial 18F-FDG uptake occurred during the second scan. It is still unclear to us why such an extremely high intraindividual variability in global myocardial 18F-FDG uptake can occur, but this variability underlines the necessity for further studies in this field. In this context, the set-up of Inglese et al. is only one side of the coin (1). The other side is to study modulation of glucose metabolism in myocytes for a better understanding of myocardial glucose metabolism (6), in particular after radiation treatment or stem cell transplantation (7).