Is work overload associated with diagnostic errors on 18F-FDG-PET/CT?

PURPOSE: To determine the association between workload and diagnostic errors on 18F-FDG-PET/CT. MATERIALS AND METHODS: This study included 103 18F-FDG-PET/CT scans with a diagnostic error that was corrected with an addendum between March 2018 and July 2023. All scans were performed at a tertiary care center. The workload of each nuclear medicine physician or radiologist who authorized the 18F-FDG-PET/CT report was determined on the day the diagnostic error was made and normalized for his or her own average daily production (workloadnormalized). A workloadnormalized of more than 100% indicates that the nuclear medicine physician or radiologist had a relative work overload, while a value of less than 100% indicates a relative work underload on the day the diagnostic error was made. The time of the day the diagnostic error was made was also recorded. Workloadnormalized was compared to 100% using a signed rank sum test, with the hypothesis that it would significantly exceed 100%. A Mann-Kendall test was performed to test the hypothesis that diagnostic errors would increase over the course of the day. RESULTS: Workloadnormalized (median of 121%, interquartile range: 71 to 146%) on the days the diagnostic errors were made was significantly higher than 100% (P = 0.014). There was no significant upward trend in the frequency of diagnostic errors over the course of the day (Mann-Kendall tau = 0.05, P = 0.7294). CONCLUSION: Work overload seems to be associated with diagnostic errors on 18F-FDG-PET/CT. Diagnostic errors were encountered throughout the entire working day, without any upward trend towards the end of the day.

The radiology job market in the Netherlands: which subspecialties and other skills are in demand?

OBJECTIVES: To evaluate the current job market for medical specialists in radiology and nuclear medicine (NM) in the Netherlands. METHODS: Vacancies posted for radiologists and nuclear medicine physicians in the Netherlands between December 2020 and February 2022 were collected and analyzed. RESULTS: A total of 157 vacancies (146 for radiologist and 11 for nuclear medicine physicians) were included. The most sought-after subspecialties were all-round (22%), abdominal (19%), and interventional radiology (14%), and 30% of vacancies preferred applicants with additional non-clinical skills (research, teaching, management, information and communications technology (ICT)/artificial intelligence (AI)). Non-academic hospitals significantly more frequently requested all-round radiologists (n = 31) than academic hospitals (n = 1) (p = 0.001), while the distribution of other requested subspecialties was not significantly different between non-academic and academic vacancies. Non-academic hospitals also significantly more frequently requested additional research tasks in their vacancies (n = 35) compared to academic hospitals (n = 4) (p = 0.011). There were non-significant trends for non-academic hospitals more frequently requesting teaching tasks in their vacancies (n =18) than academic hospitals (n = 1) (p = 0.051), and for non-academic hospitals more frequently asking for management skills (n = 11) than academic hospitals (n = 0) (p = 0.075). CONCLUSION: All-round, abdominal, and interventional radiologists are most in demand on the job market in the Netherlands. All-round radiologists are particularly sought after by non-academic hospitals, whereas nuclear radiologists who completed the Dutch integrated NM and radiology residency seem to be welcomed by hospitals searching for a nuclear medicine specialist. Finally, non-clinical skills (research, teaching, management, ICT/AI) are commonly requested. These data can be useful for residents and developers of training curricula. CLINICAL RELEVANCE STATEMENT: An overview of the radiology job market and the requested skills is important for residents, for those who seek work as a radiologist, and for those who are involved in the design and revision of residency programs. KEY POINTS: Review of job vacancies over an extended period of time provides valuable information to residents and feedback to potentially improve radiology and nuclear medicine (NM) residency programs. All-round radiologists are wanted in non-academic hospitals and nuclear radiologists (those who have completed an integrated NM-radiology curriculum) are welcomed by hospitals searching for nuclear medicine specialists in the Netherlands. There is a need to train residents in important non-clinical skills, such as research and teaching, but also management and communications technology/artificial intelligence.

Optimisation of scan duration and image quality in oncological 89Zr immunoPET imaging using the Biograph Vision PET/CT.

PURPOSE: Monoclonal antibody (mAb)-based PET (immunoPET) imaging can characterise tumour lesions non-invasively. It may be a valuable tool to determine which patients may benefit from treatment with a specific monoclonal antibody (mAb) and evaluate treatment response. For 89Zr immunoPET imaging, higher sensitivity of state-of-the art PET/CT systems equipped with silicon photomultiplier (SiPM)-based detector elements may be beneficial as the low positron abundance of 89Zr causes a low signal-to-noise level. Moreover, the long physical half-life limits the amount of activity that can be administered to the patients leading to poor image quality even when using long scan durations. Here, we investigated the difference in semiquantitative performance between the PMT-based Biograph mCT, our clinical reference system, and the SiPM-based Biograph Vision PET/CT in 89Zr immunoPET imaging. Furthermore, the effects of scan duration reduction using the Vision on semiquantitative imaging parameters and its influence on image quality assessment were evaluated. METHODS: Data were acquired on day 4 post 37 MBq 89Zr-labelled mAb injection. Five patients underwent a double scan protocol on both systems. Ten patients were scanned only on the Vision. For PET image reconstruction, three protocols were used, i.e. one camera-dependent protocol and European Association of Nuclear Medicine Research Limited (EARL) standards 1 and 2 compliant protocols. Vision data were acquired in listmode and were reprocessed to obtain images at shorter scan durations. Semiquantitative PET image parameters were derived from tumour lesions and healthy tissues to assess differences between systems and scan durations. Differently reconstructed images obtained using the Vision were visually scored regarding image quality by two nuclear medicine physicians. RESULTS: When images were reconstructed using 100% acquisition time on both systems following EARL standard 1 compliant reconstruction protocols, results regarding semiquantification were comparable. For Vision data, reconstructed images that conform to EARL1 standards still resulted in comparable semiquantification at shorter scan durations (75% and 50%) regarding 100% acquisition time. CONCLUSION: Scan duration of 89Zr immunoPET imaging using the Vision can be decreased up to 50% compared with using the mCT while maintaining image quality using the EARL1 compliant reconstruction protocol.

Dose finding study for unilobar radioembolization using holmium-166 microspheres to improve resectability in patients with HCC: the RALLY protocol.

BACKGROUND: High dose unilobar radioembolization (also termed 'radiation lobectomy')-the transarterial unilobar infusion of radioactive microspheres as a means of controlling tumour growth while concomitantly inducing future liver remnant hypertrophy-has recently gained interest as induction strategy for surgical resection. Prospective studies on the safety and efficacy of the unilobar radioembolization-surgery treatment algorithm are lacking. The RALLY study aims to assess the safety and toxicity profile of holmium-166 unilobar radioembolization in patients with hepatocellular carcinoma ineligible for surgery due to insufficiency of the future liver remnant. METHODS: The RALLY study is a multicenter, interventional, non-randomized, open-label, non-comparative safety study. Patients with hepatocellular carcinoma who are considered ineligible for surgery due to insufficiency of the future liver remnant (< 2.7%/min/m2 on hepatobiliary iminodiacetic acid scan will be included. A classical 3 + 3 dose escalation model will be used, enrolling three to six patients in each cohort. The primary objective is to determine the maximum tolerated treated non-tumourous liver-absorbed dose (cohorts of 50, 60, 70 and 80 Gy). Secondary objectives are to evaluate dose-response relationships, to establish the safety and feasibility of surgical resection following unilobar radioembolization, to assess quality of life, and to generate a biobank. DISCUSSION: This will be the first clinical study to assess the unilobar radioembolization-surgery treatment algorithm and may serve as a stepping stone towards its implementation in routine clinical practice. TRIAL REGISTRATION: Netherlands Trial Register NL8902 , registered on 2020-09-15.

The integrated nuclear medicine and radiology residency program in the Netherlands: strengths and potential areas for improvement according to nuclear medicine physicians and radiologists.

PURPOSE: To evaluate the Dutch integrated nuclear medicine and radiology residency program from the perspective of nuclear medicine physicians and radiologists. METHODS: A survey was distributed among nuclear medicine physicians and radiologists in hospitals that participate in the Dutch integrated nuclear medicine and radiology training program. RESULTS: A total of 139 completed questionnaires were included. Nuclear medicine physicians (n = 36) assigned a mean score of 5.7 ± 2.0, and radiologists (n = 103) assigned a mean score of 6.5 ± 2.8 (on a 1-10 scale) to the success of the integrated training program in their hospital. On multiple regression, female gender of the survey participant (B = 2.22, P = 0.034), musculoskeletal radiology as subspecialty of the survey participant (B = 3.36, P = 0.032), and the survey participant's expectancy of resident's ability to handle workload after completion of residency were significantly associated with perceived success of the integrated training program (B = 1.16, P = 0.023). Perceived strengths of the integrated training program included broadening of expertise, a better preparation of future imaging specialists for hybrid imaging, increased efficiency in training residents, and increased efficiency in multidisciplinary meetings. Perceived weaknesses of the integrated training program included reduced exposure to nuclear medicine, less time for research and innovation, and concerns about its international recognition. CONCLUSION: This study provided insights into the experiences of nuclear medicine physicians and radiologists with the Dutch integrated nuclear medicine and radiology residency program, which may be helpful to improve the program and similar residency programs in other countries.

EARL compliance and imaging optimisation on the Biograph Vision Quadra PET/CT using phantom and clinical data.

PURPOSE: Current European Association of Nuclear Medicine (EANM) Research Ltd. (EARL) guidelines for the standardisation of PET imaging developed for conventional systems have not yet been adjusted for long axial field-of-view (LAFOV) systems. In order to use the LAFOV Siemens Biograph Vision Quadra PET/CT (Siemens Healthineers, Knoxville, TN, USA) in multicentre research and harmonised clinical use, compliance to EARL specifications for 18F-FDG tumour imaging was explored in the current study. Additional tests at various locations throughout the LAFOV and the use of shorter scan durations were included. Furthermore, clinical data were collected to further explore and validate the effects of reducing scan duration on semi-quantitative PET image biomarker accuracy and precision when using EARL-compliant reconstruction settings. METHODS: EARL compliance phantom measurements were performed using the NEMA image quality phantom both in the centre and at various locations throughout the LAFOV. PET data (maximum ring difference (MRD) = 85) were reconstructed using various reconstruction parameters and reprocessed to obtain images at shorter scan durations. Maximum, mean and peak activity concentration recovery coefficients (RC) were obtained for each sphere and compared to EARL standards specifications. Additionally, PET data (MRD = 85) of 10 oncological patients were acquired and reconstructed using various reconstruction settings and reprocessed from 10 min listmode acquisition into shorter scan durations. Per dataset, SUVs were derived from tumour lesions and healthy tissues. ANOVA repeated measures were performed to explore differences in lesion SUVmax and SUVpeak. Wilcoxon signed-rank tests were performed to evaluate differences in background SUVpeak and SUVmean between scan durations. The coefficient of variation (COV) was calculated to characterise noise. RESULTS: Phantom measurements showed EARL compliance for all positions throughout the LAFOV for all scan durations. Regarding patient data, EARL-compliant images showed no clinically meaningful significant differences in lesion SUVmax and SUVpeak or background SUVmean and SUVpeak between scan durations. Here, COV only varied slightly. CONCLUSION: Images obtained using the Vision Quadra PET/CT comply with EARL specifications. Scan duration and/or activity administration can be reduced up to a factor tenfold without the interference of increased noise.

Head-to-head comparison between 18 F-DOPA PET/CT and 68 Ga-DOTA peptides PET/CT in detecting intestinal neuroendocrine tumours: A systematic review and meta-analysis.

PURPOSE: The imaging of intestinal neuroendocrine tumours (NETs) relies on functional positron emission tomography (PET) tracers; these tumours can be studied by means of both 68 Ga-DOTA peptides and 18 F-fluorodihydroxyphenyl- l-alanine (18 F-DOPA) PET/computed tomography (CT). As yet, it is unclear which of these two modalities offers the better sensitivity. We therefore conducted a meta-analysis to assess the available data. METHODS: PubMed, CENTRAL, Scopus and Web of Science were searched for studies comparing the sensitivity of 68 Ga-DOTA peptides and 18 F-DOPA PET/CT; papers up to February 2021 were considered. In each study, we considered sensitivity in terms of patient-based analysis (PBA), region-based analysis (RBA) and lesion-based analysis (LBA), and pooled the results yielded by each tracer. Multidisciplinary follow-up served as the standard of truth. RESULTS: Of the 636 records identified, 6 articles published between 2008 and 2021 were finally selected, and 112 intestinal NETs patients were included. The pooled sensitivity of 18 F-DOPA PET/CT was 83%, 89% and 95% on PBA, RBA and LBA, respectively. 68 Ga-DOTA peptides PET/CT showed sensitivity of 88%, 92% and 82% on PBA, RBA and LBA, respectively. No significant differences were found between the two tracers on PBA and RBA. By contrast, a clear trend towards significance in favour of 18 F-DOPA PET/CT was identified on LBA. The presence of a significant difference in favour of 18 F-DOPA PET/CT was confirmed in a subgroup analysis conducted only on the most recent and largest studies. In all three analyses, mild-to-high heterogeneity was found; however, no publication bias was observed. CONCLUSION: Both 18 F-DOPA PET/CT and 68 Ga-DOTA-peptides PET/CT are reliable diagnostic procedures in patients with intestinal NETs. However, in terms of lesion detection, a non-negligible difference in favour of 18 F-DOPA PET/CT was observed. Thus, the use of 18 F-DOPA PET/CT could be considered as a first-line molecular procedure in intestinal NETs.

Long axial field of view PET scanners: a road map to implementation and new possibilities.

In this contribution, several opportunities and challenges for long axial field of view (LAFOV) PET are described. It is an anthology in which the main issues have been highlighted. A consolidated overview of the camera system implementation, business and financial plan, opportunities and challenges is provided. What the nuclear medicine and molecular imaging community can expect from these new PET/CT scanners is the delivery of more comprehensive information to the clinicians for advancing diagnosis, therapy evaluation and clinical research.

Lutetium-177-PSMA-I&T as metastases directed therapy in oligometastatic hormone sensitive prostate cancer, a randomized controlled trial.

BACKGROUND: In recent years, there is increasing evidence showing a beneficial outcome (e.g. progression free survival; PFS) after metastases-directed therapy (MDT) with external beam radiotherapy (EBRT) or targeted surgery for oligometastatic hormone sensitive prostate cancer (oHSPC). However, many patients do not qualify for these treatments due to prior interventions or tumor location. Such oligometastatic patients could benefit from radioligand therapy (RLT) with 177Lu-PSMA; a novel tumor targeting therapy for end-stage metastatic castration-resistant prostate cancer (mCRPC). Especially because RLT could be more effective in low volume disease, such as the oligometastatic status, due to high uptake of radioligands in smaller lesions. To test the hypothesis that 177Lu-PSMA is an effective treatment in oHSPC to prolong PFS and postpone the need for androgen deprivation therapy (ADT), we initiated a multicenter randomized clinical trial. This is globally, the first prospective study using 177Lu-PSMA-I&T in a randomized multicenter setting. METHODS & DESIGN: This study compares 177Lu-PSMA-I&T MDT to the current standard of care (SOC); deferred ADT. Fifty-eight patients with oHSPC (≤5 metastases on PSMA PET) and high PSMA uptake (SUVmax > 15, partial volume corrected) on 18F-PSMA PET after prior surgery and/or EBRT and a PSA doubling time of < 6 months, will be randomized in a 1:1 ratio. The patients randomized to the interventional arm will be eligible for two cycles of 7.4GBq 177Lu-PSMA-I&T at a 6-week interval. After both cycles, patients are monitored every 3 weeks (including adverse events, QoL- and xerostomia questionnaires and laboratory testing) at the outpatient clinic. Twenty-four weeks after cycle two an end of study evaluation is planned together with another 18F-PSMA PET and (whole body) MRI. Patients in the SOC arm are eligible to receive 177Lu-PSMA-I&T after meeting the primary study objective, which is the fraction of patients who show disease progression during the study follow up. A second primary objective is the time to disease progression. Disease progression is defined as a 100% increase in PSA from baseline or clinical progression. DISCUSSION: This is the first prospective randomized clinical study assessing the therapeutic efficacy and toxicity of 177Lu-PSMA-I&T for patients with oHSPC. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04443062 .

Imaging cardiac innervation in hereditary transthyretin (ATTRm) amyloidosis: A marker for neuropathy or cardiomyopathy in case of heart failure?

BACKGROUND: Nuclear imaging modalities using 123Iodine-metaiodobenzylguanidine (123I-MIBG) and bone seeking tracers identify early cardiac involvement in ATTRm amyloidosis patients. However, little is known whether results from 123I-MIBG scintigraphy actually correlate to markers for either cardiac autonomic neuropathy or cardiomyopathy. METHODS: All TTR mutation carriers and ATTRm patients who underwent both 123I-MIBG and 99mTechnetium-hydroxymethylene diphosphonate (99mTc-HDP) scintigraphy were included. Cardiomyopathy was defined as NT-proBNP > 365 ng/L, and cardiac autonomic neuropathy as abnormal cardiovascular reflexes at autonomic function tests. Late 123I-MIBG heart-to-mediastinum ratio (HMR) < 2.0 or wash-out > 20%, and any cardiac 99mTc-HDP uptake were considered as abnormal. RESULTS: 39 patients (13 carriers and 26 ATTRm patients) were included in this study. Patients with cardiomyopathy, with or without cardiac autonomic neuropathy, had lower late HMR than similar patients without cardiomyopathy [median 1.1 (range 1.0-1.5) and 1.5(1.2-2.6) vs 2.4 (1.4-3.8) and 2.5 (1.5-3.7), respectively, P < 0.001]. Late HMR and wash-out (inversely) correlated with NT-proBNP r = - 0.652 (P < 0.001) and r = 0.756 (P < 0.001), respectively. Furthermore, late HMR and wash-out (inversely) correlated with cardiac 99mTc-HDP uptake r = - 0.663 (P < 0.001) and r = 0.617 (P < 0.001), respectively. CONCLUSION: In case of heart failure, 123I-MIBG scintigraphy reflects cardiomyopathy rather than cardiac autonomic neuropathy in ATTRm patients and TTR mutation carriers. 123I-MIBG scintigraphy may already be abnormal before any cardiac bone tracer uptake is visible.

Adrenal tracer uptake by 18F-FDOPA PET/CT in patients with pheochromocytoma and controls.

CONTEXT: 18F-FDOPA PET/CT accurately localizes pheochromocytoma in patients with an established biochemical diagnosis. However, cut-off 18F-FDOPA levels of standardized uptake values (SUVmax) for both normal adrenal glands and pheochromocytoma are lacking. OBJECTIVE: Objectives of this study were to determine (1) reference maximum standardized uptake values (SUVmax) for normal adrenal 18F-DOPA tracer uptake and (2) the optimal diagnostic approach for pheochromocytoma localization by using 18F-DOPA SUVmax across a series of cut-off points: the affected adrenal gland (inter-individual analysis), the difference in SUVmax between the affected adrenal gland and the contralateral normal adrenal gland (intra-individual analysis), or a combination of these two. PATIENTS AND METHODS: All patients with histologically confirmed pheochromocytoma diagnosed at our center between November 2009 and December 2017 were retrospectively analysed. Only those patients who underwent an 18F-FDOPA PET/CT-scan for localization purposes before adrenalectomy were included for further analysis. The control group consisted of patients who underwent 18F-FDOPA PET/CT for other indications and who had no genetic susceptibility for developing a pheochromocytoma. SUVmax of the volume of interest surrounding the adrenal glands was determined on EARL reconstructed images. Receiver operating characteristic (ROC) analysis was performed for adrenal gland SUVmax and intra-individual difference in SUVmax between affected and normal adrenal gland. In addition, binary logistic regression was performed for ROC analysis of the combined parameters. RESULTS: In total, 47 histologically confirmed pheochromocytomas were diagnosed in 45 patients, and 245 disease control patients were identified. In the control group, no statistical differences between the SUVmax of left and right adrenal glands were observed, and uptake values in both adrenal glands correlated significantly with each other (r = 0.865, p < 0.001). Median (range) adrenal gland SUVmax in pheochromocytomas and in the control group was 12 (2.6-50) and 2.9 (1.1-6.6), respectively (p < 0.001). ROC analysis revealed 93% sensitivity and 85% specificity at an SUVmax cut-off value of 4.1 (area under the curve (AUC) = 0.951), and 93% sensitivity and 96% specificity at an intra-individual SUVmax difference between the affected and normal adrenal gland of 1.0 (AUC = 0.992). The combination of both variables increased the AUC to 0.995. CONCLUSIONS: 18F-FDOPA PET/CT distinguishes pheochromocytoma from normal adrenal glands with the highest diagnostic accuracy when combining the SUVmax of the affected adrenal gland with the difference in SUVmax between affected and normal adrenal gland.

Tumour necrosis as assessed with 18F-FDG PET is a potential prognostic marker in diffuse large B cell lymphoma independent of MYC rearrangements.

OBJECTIVES: MYC gene rearrangements in diffuse large B cell lymphomas (DLBCLs) result in high proliferation rates and are associated with a poor prognosis. Strong proliferation is associated with high metabolic demand and tumour necrosis. The aim of this study was to investigate differences in the presence of necrosis and semiquantitative 18F-FDG PET metrics between DLBCL cases with or without a MYC rearrangement. The prognostic impact of necrosis and semiquantitative 18F-FDG PET parameters was investigated in an explorative survival analysis. METHODS: Fluorescence in situ hybridisation analysis for MYC rearrangements, visual assesment, semiquantitative analysis of 18F-FDG PET scans and patient survival analysis were performed in 61 DLBCL patients, treated at a single referral hospital between 2008 and 2015. RESULTS: Of 61 tumours, 21 (34%) had a MYC rearrangement (MYC+). MYC status was neither associated with the presence of necrosis on 18F-FDG PET scans (necrosisPET; p = 1.0) nor associated with the investigated semiquantitative parameters maximum standard uptake value (SUVmax; p = 0.43), single highest SUVmax (p = 0.49), metabolic active tumour volume (MATV; p = 0.68) or total lesion glycolysis (TLG; p = 0.62). A multivariate patient survival analysis of the entire cohort showed necrosisPET as an independent prognostic marker for disease-specific survival (DSS) (HR = 13.9; 95% CI 3.0-65; p = 0.001). CONCLUSIONS: MYC rearrangements in DLBCL have no influence on the visual parameter necrosisPET or the semi-quantiative parameters SUVmax, MATV and TLG. Irrespective of MYC rearrangements, necrosisPET is an independent, adverse prognostic factor for DSS. KEY POINTS: • Retrospective analysis indicates that MYC rearrangement is not associated with necrosis on 18 F-FDG PET (necrosis PET ) scans or semiquantitative 18 F-FDG PET parameters. • Necrosis PET is a potential independent adverse prognostic factor for disease-specific survival in patients with DLBCL and is not influenced by the presence of MYC rearrangements.

Imaging cardiac innervation in amyloidosis.

Cardiac amyloidosis is a form of restrictive cardiomyopathy resulting in heart failure and potential risk on arrhythmia, due to amyloid infiltration of the nerve conduction system and the myocardial tissue. The prognosis in this progressive disease is poor, probably due the development of cardiac arrhythmias. Early detection of cardiac sympathetic innervation disturbances has become of major clinical interest, because its occurrence and severity limits the choice of treatment. The use of iodine-123 labelled metaiodobenzylguanidine ([I-123]MIBG), a chemical modified analogue of norepinephrine, is well established in patients with heart failure and plays an important role in evaluation of sympathetic innervation in cardiac amyloidosis. [I-123]MIBG is stored in vesicles in the sympathetic nerve terminals and is not catabolized like norepinephrine. Decreased heart-to-mediastinum ratios on late planar images and increased wash-out rates indicate cardiac sympathetic denervation and are associated with poor prognosis. Single photon emission computed tomography provides additional information and has advantages for evaluating abnormalities in regional distribution in the myocardium. [I-123]MIBG is mainly useful in patients with hereditary and wild-type ATTR cardiac amyloidosis, not in AA and AL amyloidosis. The potential role of positron emission tomography for cardiac sympathetic innervation in amyloidosis has not yet been identified.

Phase analysis of gated PET in the evaluation of mechanical ventricular synchrony: A narrative overview.

Noninvasive imaging modalities offer the possibility to dynamically evaluate cardiac motion during the cardiac cycle by means of ECG-gated acquisitions. Such motion characterization along with orientation, segmentation preprocessing, and ultimately, phase analysis, can provide quantitative estimates of ventricular mechanical synchrony. Current evidence on the role of mechanical synchrony evaluation is mainly available for echocardiography and gated single-photon emission computed tomography, but less is known about the utilization of gated positron emission tomography (PET). Although data available are sparse, there is indication that mechanical synchrony evaluation can be of diagnostic and prognostic values in patients with known or suspected coronary artery disease-related myocardial ischemia, prediction of response to cardiac resynchronization therapy, and estimation of risk for adverse cardiac events in patients' heart failure. As such, the evaluation of mechanical ventricular synchrony through phase analysis of gated acquisitions represents a value addition to modern cardiac PET imaging modality, which warrants further research and development in the evaluation of patients with cardiovascular disease.

Avenues to molecular imaging of dying cells: Focus on cancer.

Successful treatment of cancer patients requires balancing of the dose, timing, and type of therapeutic regimen. Detection of increased cell death may serve as a predictor of the eventual therapeutic success. Imaging of cell death may thus lead to early identification of treatment responders and nonresponders, and to "patient-tailored therapy." Cell death in organs and tissues of the human body can be visualized, using positron emission tomography or single-photon emission computed tomography, although unsolved problems remain concerning target selection, tracer pharmacokinetics, target-to-nontarget ratio, and spatial and temporal resolution of the scans. Phosphatidylserine exposure by dying cells has been the most extensively studied imaging target. However, visualization of this process with radiolabeled Annexin A5 has not become routine in the clinical setting. Classification of death modes is no longer based only on cell morphology but also on biochemistry, and apoptosis is no longer found to be the preponderant mechanism of cell death after antitumor therapy, as was earlier believed. These conceptual changes have affected radiochemical efforts. Novel probes targeting changes in membrane permeability, cytoplasmic pH, mitochondrial membrane potential, or caspase activation have recently been explored. In this review, we discuss molecular changes in tumors which can be targeted to visualize cell death and we propose promising biomarkers for future exploration.

Prediction of Response to Neoadjuvant Chemotherapy and Radiation Therapy with Baseline and Restaging 18F-FDG PET Imaging Biomarkers in Patients with Esophageal Cancer.

Purpose To assess the value of baseline and restaging fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) radiomics in predicting pathologic complete response to neoadjuvant chemotherapy and radiation therapy (NCRT) in patients with locally advanced esophageal cancer. Materials and Methods In this retrospective study, 73 patients with histologic analysis-confirmed T1/N1-3/M0 or T2-4a/N0-3/M0 esophageal cancer were treated with NCRT followed by surgery (Chemoradiotherapy for Esophageal Cancer followed by Surgery Study regimen) between October 2014 and August 2017. Clinical variables and radiomic features from baseline and restaging 18F-FDG PET were selected by univariable logistic regression and least absolute shrinkage and selection operator. The selected variables were used to fit a multivariable logistic regression model, which was internally validated by using bootstrap resampling with 20 000 replicates. The performance of this model was compared with reference prediction models composed of maximum standardized uptake value metrics, clinical variables, and maximum standardized uptake value at baseline NCRT radiomic features. Outcome was defined as complete versus incomplete pathologic response (tumor regression grade 1 vs 2-5 according to the Mandard classification). Results Pathologic response was complete in 16 patients (21.9%) and incomplete in 57 patients (78.1%). A prediction model combining clinical T-stage and restaging NCRT (post-NCRT) joint maximum (quantifying image orderliness) yielded an optimism-corrected area under the receiver operating characteristics curve of 0.81. Post-NCRT joint maximum was replaceable with five other redundant post-NCRT radiomic features that provided equal model performance. All reference prediction models exhibited substantially lower discriminatory accuracy. Conclusion The combination of clinical T-staging and quantitative assessment of post-NCRT 18F-FDG PET orderliness (joint maximum) provided high discriminatory accuracy in predicting pathologic complete response in patients with esophageal cancer. © RSNA, 2018 Online supplemental material is available for this article.

Clinical value of quantitative measurements derived from GATED SPECT: motion and thickening, volumes and related LVEF.

Radionuclide myocardial perfusion imaging using ECG-gated acquisition with single photon emission computed tomography (gated SPECT) is the current state of the art imaging modality for symptomatic patients with known or at least indeterminate likelihood of coronary artery disease. Gated SPECT provides a wide variety of additional information about left ventricular (LV) function measurements, for example LV volumes, ejection fraction (LVEF) and regional wall motion abnormalities. This contributes to a higher diagnostic accuracy, additional prognostic information and predicting benefit from revascularization in these patients. Gated SPECT is an easily reproducible and accurate tool, which provides additional information to myocardial perfusion, regarding functional LV data. Assessment of LV wall motion, volumes and LVEF increases diagnostic accuracy and has prognostic and predictive value for the individual patient.

Sympathetic denervation in patients with ischemic cardiomyopathy and risk on ventricular tachy-arrhythmias. A pilot study.

BACKGROUND: Patients with ischemic cardiomyopathy (ICM) are at risk for ventricular arrhythmias and are protected by an implantable cardioverter defibrillator (ICD). Visualization of cardiac sympathetic innervation may play an additional role to left ventricular ejection fraction (LVEF) in identifying those patients who will benefit from ICD therapy. The purpose of this study was to detect the role of sympathetic denervation in the genesis of ventricular arrhythmias in ICM patients. METHODS: Twenty patients with ICM and LVEF <30% were included in this pilot study. Included patients were equally stratified into two groups: no history of arrhythmias (group A) and recurrent arrhythmias (group B). All patients underwent cardiac sympathetic denervation (using carbon-11 labelled meta-hydroxy-ephedrine ([11C]-mHED)), myocardial ischemia and viability detection. Patients were followed up to one year after the imaging studies. RESULTS: Mean age was 63±7.5 years. Mean global retention of [11C]-mHED was 0.055±0,012 min-1, and was not different between the two patient groups: 0.056±0.011 min-1 vs. 0.054±0.013 min-1 for group A vs. group B, respectively. During follow-up, seven patients developed ventricular arrhythmias, and four patients died. No difference in [11C]-mHED retention was found between patients with and without ventricular arrhythmia during follow-up. However, size of denervated area was larger in patients who died during follow-up: 10±1 segments vs. 6±2 segments, P=0.002. CONCLUSIONS: Cardiac sympathetic innervation is impaired in patients with ischemic cardiomyopathy. All-cause mortality occurred in those patients with large areas of [11C]-mHED defect.

Retracted: Diagnosis and Treatment of Intestinal Melanoma Metastases in the Era of Effective Systemic Treatment.

OBJECTIVE: The aim of the present study was to describe different presentations, diagnostic tools, and available treatments for melanoma metastasized to the intestines. BACKGROUND: The intestine is a frequent site of metastases in melanoma patients. In the current era, with long-term survival after systemic treatment, there is a need for a timely diagnosis and optimal treatment of intestinal metastases. METHODS: Patients diagnosed between 2011 and 2015 with intestinal metastases of melanoma were included. Diagnostic procedures, treatment strategies, and their outcome were analyzed for all patients. RESULTS: A total of 22 patients were included. Twenty patients received systemic therapy for widely disseminated disease. Fourteen of these twenty patients received local treatment for symptomatic intestinal metastases. Median overall survival after detection of intestinal metastasis in patients receiving systemic treatment was 22 months. On the basis of this cohort, a treatment algorithm for treatment of patients with symptomatic intestinal melanoma metastases was constructed. CONCLUSIONS: The treatment of intestinal melanoma metastases has changed due to the introduction of novel systemic treatments that can result in long-term survival of patients with widely metastatic melanoma. Surgeons and other clinicians should be aware of these changes in clinical practice as well as the diverse presentation of intestinal melanoma metastases and the diagnostic and therapeutic dilemmas involved.