Comparison of cardio-focal and chest reconstruction of technetium-99m pyrophosphate scintigraphy for diagnosis of transthyretin cardiac amyloidosis: a quality assurance study.

BACKGROUND: SPECT improves diagnostic specificity of Technetium-99m pyrophosphate (PYP) scintigraphy. Diagnostic performance of PYP data, reconstructed as either chest or cardio-focal SPECT is not known. METHODS: In this quality assurance study, blinded evaluation of PYP SPECT/CT data from 102 Caucasian patients (mean age 76 ± 11 years, 67% men) was performed by two readers. Reader 1 reviewed planar and PYP chest SPECT, while reader 2 reviewed planar and cardio-focal PYP SPECT. Demographic, clinical, and other testing data were obtained from the electronic medical records. RESULTS: A total of 41 patients (40%) were considered positive based on myocardial uptake on chest PYP SPECT. Of these, 98% of the patients had a Perugini score ≥ 2 on planar imaging. There was good agreement between the two readers for visual score ≥ 2 (k = .88, P < .001) and excellent agreement for myocardial uptake on tomographic imaging (98%, P < .001). Only one study was categorized as false negative by cardio-focal SPECT reconstruction. Non-diffuse myocardial uptake was identified in 22% of those with a positive PYP SPECT. CONCLUSION: When read by experienced readers, chest and cardio-focal reconstruction of PYP SPECT have comparable diagnostic performance. A substantial proportion of patients with a positive PYP SPECT have a non-diffuse distribution of PYP. Given the possibility of misclassification of non-diffuse myocardial uptake on cardio-focal reconstruction alone, chest reconstruction of PYP scintigraphy should be strongly considered.

Intra-individual comparison of 18F-sodium fluoride PET-CT and 99mTc bone scintigraphy with SPECT in patients with prostate cancer or breast cancer at high risk for skeletal metastases (MITNEC-A1): a multicentre, phase 3 trial.

BACKGROUND: Detection of skeletal metastases in patients with prostate cancer or breast cancer remains a major clinical challenge. We aimed to compare the diagnostic performance of 99mTc-methylene diphosphonate (99mTc-MDP) single-photon emission CT (SPECT) and 18F-sodium fluoride (18F-NaF) PET-CT for the detection of osseous metastases in patients with high-risk prostate or breast cancer. METHODS: MITNEC-A1 was a prospective, multicentre, single-cohort, phase 3 trial conducted in ten hospitals across Canada. Patients aged 18 years or older with breast or prostate cancer with a WHO performance status of 0-2 and with high risk or clinical suspicion for bone metastasis, but without previously documented bone involvement, were eligible. 18F-NaF PET-CT and 99mTc-MDP SPECT were done within 14 days of each other for each participant. Two independent reviewers interpreted each modality without knowledge of other imaging findings. The primary endpoint was the overall accuracy of 99mTc-MDP SPECT and 18F-NaF PET-CT scans for the detection of bone metastases in the per-protocol population. A combination of histopathological, clinical, and imaging follow-up for up to 24 months was used as the reference standard to assess the imaging results. Safety was assessed in all enrolled participants. This study is registered with ClinicalTrials.gov, NCT01930812, and is complete. FINDINGS: Between July 11, 2014, and March 3, 2017, 290 patients were screened, 288 of whom were enrolled (64 participants with breast cancer and 224 with prostate cancer). 261 participants underwent both 18F-NaF PET-CT and 99mTc-MDP SPECT and completed the required follow-up for statistical analysis. Median follow-up was 735 days (IQR 727-750). Based on the reference methods used, 109 (42%) of 261 patients had bone metastases. In the patient-based analysis, 18F-NaF PET-CT was more accurate than 99mTc-MDP SPECT (84·3% [95% CI 79·9-88·7] vs 77·4% [72·3-82·5], difference 6·9% [95% CI 1·3-12·5]; p=0·016). No adverse events were reported for the 288 patients recruited. INTERPRETATION: 18F-NaF has the potential to displace 99mTc-MDP as the bone imaging radiopharmaceutical of choice in patients with high-risk prostate or breast cancer. FUNDING: Canadian Institutes of Health Research.

Refractory Epilepsy: The Role of Positron Emission Tomography.

RATIONALE: Presurgical localization of the epileptogenic focus is critical to successful surgery. Traditionally, localization of the epileptogenic focus depends on seizure semiology, scalp video-electroencephalography (vEEG), magnetic resonance imaging (MRI), neuropsychological assessment, and, when needed, intracranial EEG (iEEG). We aimed to explore the role of positron emission tomography (PET) in the presurgical evaluation of patients with refractory epilepsy. METHODS: A retrospective review was conducted on patients from London Health Sciences Centre (London, Ontario) with refractory epilepsy who underwent PET from September of 2011 to April of 2016. The accuracy of epileptogenic focus localization was compared between different investigative modalities (MRI, vEEG, iEEG, PET), and the outcomes were documented, including seizure freedom after surgical resection, improvement of seizure frequency, guidance for further investigations, and exclusion of patients from further evaluation. Patients who underwent surgery were followed up at 3 months and onward. RESULTS: We identified 62 patients with refractory epilepsy who underwent PET. The mean age was 34 years (range=20-68). A total of 36 had concordant PET and vEEG findings: 6 had surgical resection and either became seizure-free (29.4%) or had improvement in seizure frequency (5.9%) at 3 months; 11 had surgical resection and either became seizure-free (29.4%) or had improvement in seizure frequency (35.3%) at 3 months, but required iEEG for final verification. CONCLUSIONS: PET has an important role in presurgical evaluation of patients with refractory epilepsy. It may allow resection of the epileptogenic focus without the need for iEEG, guiding intracranial electrode placement for further localization of the epileptogenic focus, or exclusion of patients from further evaluation.

Very high coronary artery calcium score with normal myocardial perfusion SPECT imaging is associated with a moderate incidence of severe coronary artery disease.

PURPOSE: Myocardial perfusion imaging (MPI) has limitations in the presence of balanced multivessel disease (MVD) and left main (LM) coronary artery disease, occasionally resulting in false-normal results despite the high cardiovascular risk associated with this condition. The purpose of this study was to assess the incidence of severe coronary artery disease (CAD) in the presence of a very high Agatston coronary artery calcium (CAC) score (>1,000) in stable symptomatic patients without known CAD but with normal MPI results. METHODS: A total of 2,659 prospectively acquired consecutive patients were referred for MPI and evaluation of CAC score by CT. Of this patient population, 8 % (222/2,659) had ischemia without myocardial infarction (MI) on MPIand 11 % (298/2,659) had abnormal MPI (MI and/or ischemia). On presentation 1 % of the patients (26/2,659) were symptomatic, had a CAC score >1,000 and normal MPI results. The definition of normal MPI was strict and included a normal hemodynamic response without ischemic ECG changes and normal imaging, particularly absence of transient ischemic dilation. All of these 26 patients with a CAC score >1,000 and normal MPI findings underwent cardiac catheterization. RESULTS: Of these 26 patients, 58 % (15/26) had severe disease (≥70 % stenosis) leading to revascularization. Of this group, 47 % (7/15) underwent percutaneous intervention, and 53 % (8/15) underwent coronary artery bypass grafting. All of these 15 patients had either MVD (14/15) or LM coronary artery disease (1/15), and represented 0.6 % (15/2,659) of all referred patients (95 % CI 0.3 - 0.9 %). The majority, 90 % (8/9), had severe CAD with typical chest pain. CONCLUSION: A very high CAC score (>1,000) with normal MPI in a small subset of symptomatically stable patients was associated with a moderate incidence of severe CAD (95 % CI 37 - 77 %). Larger studies and/or a meta-analysis of small studies are needed to more precisely estimate the incidence of CAD in this population. This study also supports the concept that a normal MPI result in patients with severe CAD may be due to balanced MVD.

Risk Stratification in Cardiac Sarcoidosis With Cardiac Positron Emission Tomography: A Systematic Review and Meta-Analysis.

BACKGROUND: Although positron emission tomography (PET) imaging is well established for its diagnostic role in cardiac sarcoidosis, less is known about the prognostic value of PET and its use in risk stratification for major adverse cardiac events (MACE). OBJECTIVES: The goal of this study was to perform a systematic review and meta-analysis looking at the prognostic value of PET imaging in patients with cardiac sarcoidosis. METHODS: Study investigators systematically searched EMBASE (Excerpta Medica dataBASE), MEDLINE, PubMed, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL (Cumulative Index to Nursing and Allied Health Literature), ClinicalTrials.gov, and the European Union Clinical Trial Registry for cardiac sarcoidosis and PET imaging. The primary outcome of interest was MACE. RESULTS: The search revealed 3,010 records, of which 55 studies were included. This represented 5,250 patients. Factors associated with MACE included the following: the combination of abnormal fluorodeoxyglucose (FDG) uptake and perfusion defect, which had an OR of 2.86 (95% CI: 1.74-4.71; P < 0.0001); abnormal perfusion or FDG uptake, which had an OR of 2.69 (95% CI: 1.67-4.33); abnormal FDG uptake, which had an OR of 2.61 (95% CI: 1.51-4.50); focal abnormal right ventricular uptake, which had an OR of 6.27 (95% CI: 3.19-12.32; P < 0.00001); and a lack of response to immunosuppression on serial PET, which had an OR of 8.43 (95% CI: 3.25-21.85; P < 0.0001). A QUIPS (Quality in Prognostic Studies) tool analysis found a low to moderate risk of bias, particularly given the small sample sizes in the individual studies. CONCLUSIONS: Multiple cardiac PET parameters provide risk stratification value in cardiac sarcoidosis. Focal right ventricular uptake and a lack of response to immunosuppressive therapy on serial PET imaging were particularly predictive of MACE.

Prognostic value of coronary computed tomography angiography compared to radionuclide myocardial perfusion imaging in patients With coronary stents.

Objectives: The aim of this study is to compare the prognostic value of coronary computed tomography angiography (CCTA) with single-photon emission computed tomography (SPECT) in predicting cardiovascular events in patients with stents. Design: Retrospective analysis. Setting: University Hospital, London, Ontario Canada. Participants: Between January 2007 and December 2018, 119 patients post-percutaneous coronary intervention (PCI) who were referred for hybrid imaging with CTA and 2-day rest/stress SPECT were enrolled. Primary and secondary outcome measures: Patients were followed for any major adverse cardiovascular event (MACE) including: All-cause mortality, Non-fatal myocardial infarction (MI), Unplanned revascularization, Cerebrovascular accident and hospitalization for arrhythmia or heart failure. We define hard cardiac events (HCE) as: cardiac death, non-fatal MI or unplanned revascularization. We used two cut-off values to define obstructive lesions with CCTA ≥50% and ≥70% in any coronary segment. SPECT scan defined as abnormal in the presence of >5% reversible myocardial perfusion defect. Results: During the follow-up period of 7.2 ± 3.4 years. 45/119 (37.8%) patients experienced 57 MACE: Ten deaths (2 cardiac deaths and 8 of non-cardiac deaths), 29 acute coronary syndrome including non-fatal MI (25 required revascularization), 7 hospitalizations for heart failure, 6 cerebrovascular accidents and 5 new atrial fibrillation. 31 HCEs were reported. Cox regression analysis showed that obstructive coronary stenosis (≥50% and ≥70%) and abnormal SPECT were associated of MACE (p = 0.037, 0.018 and 0.026), respectively. In contrast, HCEs were significantly associated with obstructive coronary stenosis of ≥50% and ≥70% with p = 0.004 and p = 0.007, respectively. In contrast, abnormal SPECT was a nonsignificant predictor of HCEs (p = 0.062). Conclusion: Obstructive coronary artery stenosis on CCTA can predict MACE and HCE. However, abnormal SPECT can only predict MACE but not HCE in patients post-PCI with a follow-up period of approximately 7 years.

SPECT/CT versus planar imaging to determine treatment strategy for non-small-cell lung cancer: a cost-effectiveness analysis.

Aim: SPECT/CT has been found to improve predicted postoperative forced expiratory volume in one second (ppoFEV1) assessments in patients with non-small-cell lung cancer (NSCLC). Methods: An economic simulation was developed comparing the cost-effectiveness of SPECT/CT versus planar scintigraphy for a US payer. Clinical outcomes and cost data were obtained through review of the published literature. Results: SPECT/CT increased the accuracy ppoFEV1 assessment, changing the therapeutic decision for 1.3% of nonsurgical patients to a surgical option, while 3.3% of surgical patients shifted to more aggressive procedures. SPECT/CT led to an expected cost of $4694 per life year gained, well below typical thresholds. Conclusion: SPECT/CT resulted in substantially improved health outcomes and was found to be highly cost-effective.

Complementary role of computed tomography angiography with fixed perfusion defects on SPECT myocardial perfusion imaging.

PURPOSE: We present this case series exploring the complementary role of coronary computed tomography angiography (CCTA) to SPECT myocardial perfusion imaging (MPI) in the detection of myocardial necrosis. METHODS: A cardiac hybrid imaging database search identified 144 patients with a previous history of ST-segment elevation myocardial infarction treated with coronary revascularization. CCTA and MPI scans were evaluated to determine whether CCTA had an added value to MPI in detecting myocardial necrosis. RESULTS: Five patients with patent stents and/or bypass grafts and both fixed perfusion defects on MPI and sub-endocardial hypo-perfusion on CCTA were identified. The extent and location of the perfusion defects were closely correlated between the CCTA and SPECT MPI images. CONCLUSION: In this series, CCTA and SPECT MPI were found to play a complementary role in the assessment of fixed perfusion defect, with CCTA adding specificity to the diagnosis of myocardial necrosis.

Survival predictors of 177Lu-Dotatate peptide receptor radionuclide therapy (PRRT) in patients with progressive well-differentiated neuroendocrine tumors (NETS).

PURPOSE: 177Lu-Dotatate is an emerging treatment modality for patients with unresectable or metastatic well-differentiated NETs. This study examines survival predictors in patients who received 177Lu-Dotatate. METHODS: A retrospective single-center review was conducted, examining 47 individuals with progressive well-differentiated NETs treated with 177Lu-Dotatate (four induction cycles of 5.5 GBq at 10-week intervals followed by eight maintenance cycles of 3.7 GBq at 6-month intervals). RESULTS: Median follow-up was 63.1 months with a median progression-free survival (PFS) of 34.1 months. However, median overall survival (OS) was not reached at the time of analysis. The presence of ≥ 5 bone metastases (hazard ratio HR 4.33; p = 0.015), non-gastroenteropancreatic (non-GEP) NETs (HR 3.22; p = 0.025) and development of interim ascites (HR 3.15; p = 0.047) independently predicted a worse OS. Patients with chromogranin A of ≥ 4 × upper limit of normal (ULN) had shorter OS (p < 0.001) and PFS (p = 0.004). Similarly, those with pre-existing ascites demonstrated a worse OS (p = 0.009) and PFS (p = 0.026). Liver metastases involving greater than 50% liver volume and the existence of unusual metastatic locations had a negative impact on OS (p = 0.033) and PFS (p = 0.026), respectively. CONCLUSION: High burden of skeletal and hepatic metastases, non-GEP-NETs, chromogranin A of ≥ 4 × ULN, unusual metastatic sites, pre-existing and interim ascites are predictors of poor outcomes in patients treated with 177Lu-Dotatate. These common indicators can be used for the risk stratification and identification of patients most likely to benefit from PRRT. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02236910, Retrospectively registered on September, 2014.

The value of 99mTc-sestamibi single-photon emission computed tomography-computed tomography in the evaluation and risk stratification of renal masses.

INTRODUCTION: Differentiation of renal cell carcinoma (RCC) from oncocytoma is a common diagnostic dilemma. A few studies have shown that 99mTc-sestamibi (MIBI) imaging has the potential to characterize indeterminate renal masses. This comparative study evaluated the utility of MIBI single-photon emission computed tomography-computed tomography (SPECT-CT) in the assessment and risk stratification of renal masses. METHODS: A total of 29 patients with 31 renal masses who had cross-sectional imaging and MIBI SPECT-CT were included. Lesions were categorized as either MIBI-positive or -negative on SPECT-CT. Individual lesion density ranged from 22-56 Hounsfield units (HU) on the non-contrast CT part of SPECT-CT. Quantitative relative MIBI uptake was calculated by measuring tumor to ipsilateral renal parenchymal uptake. The imaging results were correlated with histopathology. RESULTS: All oncocytic lesions, including seven oncocytomas and one hybrid oncocytic chromophobe tumor (100%), were positive on MIBI. One chromophobe RCC showed low-grade MIBI uptake. The remaining RCC subtypes, including 15 clear-cell, four papillary, two mixed clear-cell and papillary, and one chromophobe, were MIBI-negative. The quantitative relative tumor uptake showed statistically significant higher uptake in the low-risk/oncocytic lesions compared to RCCs. CONCLUSIONS: This study demonstrates that MIBI SPECT-CT is valuable in the characterization of indeterminate renal masses. The combination of MIBI uptake on SPECT and lesion density on non-contrast CT can be used for risk stratification of renal masses. This technique may reduce the need for further imaging (multiphasic CT or magnetic resonance imaging), renal mass biopsy, or surgical resection of low-risk renal masses. Subsequently, more patients could be followed with active surveillance.

Internal Jugular Vein and Cerebral Venous Sinus Infective Thrombophlebitis Detected With 99mTc-HMPAO White Blood Cell Scintigraphy.

ABSTRACT: A 35-year-old man with a history of renal transplant, congenital cystinosis, and diabetes was admitted to the hospital with fever, bilateral parotid gland swelling, and acute renal failure. He had 99mTc-HMPAO-WBC (99mTc-hexamethylpropyleneamineoxime white blood cell) imaging for the evaluation of possible parotitis. There was intense radiopharmaceutical uptake along the right internal jugular vein extending to the right sigmoid and transverse and superior sagittal sinuses, suggestive of infective thrombophlebitis or Lemierre syndrome. This study illustrates the value of 99mTc-HMPAO-WBC imaging as a tool for evaluating thrombophlebitis, particularly in patients with renal failure in whom contrast-enhanced CT may not be possible.

Coronary artery calcium progression after coronary artery bypass grafting surgery.

OBJECTIVES: Accelerated atherosclerosis is a well-established phenomenon after coronary artery bypass grafting surgery (CABG). In this study, we analysed coronary artery calcium (CCS) progression after CABG. METHODS: We retrospectively measured the CCS Agatston score (AS), volume score (VS) and mass score (MS) of 39 patients before and after CABG. The annualised CCS change and annualised CCS percent change of each coronary artery, coronary artery segments proximal and distal to anastomosis were analysed. RESULTS: Mean age at the time of the surgery was 59.8±8.5 years. Follow-up period between the first and second CT scans was 6.7±2.8 (range, 1.1-12.8) years. Annualised CCS percent change (AS, VS and MS) of the coronary segments proximal-to-anastomosis did not differ from that of the non-grafted coronary arteries as follow: segments proximal-to-anastomosis: median (Q1-Q3) 12.8 (5.0-37.4), 13.7 (6.1-41.1) and 14.9 (5.4-53.7), left main coronary artery 12.6 (7.4-43.8), 22.0 (8.1-44.4) and 18.2 (7.3-57.4), non-grafted left circumflex artery: 13.5 (4.4-38.1), 10.5 (2.9-45.2) and 11.5 (7.1-47.9) and non-grafted right coronary artery: 31.4 (14.4-74.5), 25.2 (16.7-62.0) and 31.3 (23.8-85.6), respectively. Likewise, annualised percent change (AS, VS and MS) was similar between the native coronary arteries. Multivariate regression analysis showed that diabetes mellitus was the only predictor of annualised percent progression of the total CCS of >15% (HR, 8.12; 95% CI, 1.05 to 26.6; p=0.04). CONCLUSION: The CCS post-CABG did not follow an accelerated progression process. Among coronary artery disease risk factors, diabetes mellitus is the only predictor of annualised CCS percent progression of >15% post-CABG.

Hiatal hernia after robotic-assisted coronary artery bypass graft surgery.

BACKGROUND: The aim of the present study is to determine the incidence/progression of hiatal hernia (HH) after robotic-assisted coronary artery bypass grafting (RA-CABG) surgery. METHODS: We reviewed the pre- and post-operative computed tomography (CT) of 491 patients who underwent RA-CABG between 2000 and 2017. Post-operative CT was acquired prospectively in a research protocol. CT was reviewed to assess the presence and the size of HH. RESULTS: We found 444/491 (90.4%) had pre-operative CT, while 201/491 (40.9%) had post-operative CT. In total, 155/491 (31.6%) had both pre- and long-term post-operative CT with a mean follow-up of 6.2 (±3.5) years. HH was more prevalent on post-operative CT, 64/155 (41.3%) compared to pre-operative CT, 44/155 (28.4%), P<0.0001. The diameter of pre-existing HH 2.8 (±1.8) cm was significantly greater after surgery 3.9 (±2.5) cm, P<0.0001. As well the volume of the pre-existing HH 5.8 (4.4-9.2) mL (quartile) was significantly greater after surgery 14.1 (7.2-64.9) mL, P<0.0001. 20/155 (12.9%) had a newly developed HH after RA-CABG. A binary multivariate regression including HH risk factors showed that male gender is a predictor of developing a HH after RA-CABG with Hazard Ratio of 3.038, confidence interval (1.10-8.43), P=0.033. CONCLUSIONS: RA-CABG is associated with an increased risk of developing HH and increases the size of pre-existing HH.

18F-FDG PET-guided diffusion tractography reveals white matter abnormalities around the epileptic focus in medically refractory epilepsy: implications for epilepsy surgical evaluation.

BACKGROUND: Hybrid PET/MRI can non-invasively improve localization and delineation of the epileptic focus (EF) prior to surgical resection in medically refractory epilepsy (MRE), especially when MRI is negative or equivocal. In this study, we developed a PET-guided diffusion tractography (PET/DTI) approach combining 18F-fluorodeoxyglucose PET (FDG-PET) and diffusion MRI to investigate white matter (WM) integrity in MRI-negative MRE patients and its potential impact on epilepsy surgical planning. METHODS: FDG-PET and diffusion MRI of 14 MRI-negative or equivocal MRE patients were used to retrospectively pilot the PET/DTI approach. We used asymmetry index (AI) mapping of FDG-PET to detect the EF as brain areas showing the largest decrease in FDG uptake between hemispheres. Seed-based WM fiber tracking was performed on DTI images with a seed location in WM 3 mm from the EF. Fiber tractography was repeated in the contralateral brain region (opposite to EF), which served as a control for this study. WM fibers were quantified by calculating the fiber count, mean fractional anisotropy (FA), mean fiber length, and mean cross-section of each fiber bundle. WM integrity was assessed through fiber visualization and by normalizing ipsilateral fiber measurements to contralateral fiber measurements. The added value of PET/DTI in clinical decision-making was evaluated by a senior neurologist. RESULTS: In over 60% of the patient cohort, AI mapping findings were concordant with clinical reports on seizure-onset localization and lateralization. Mean FA, fiber count, and mean fiber length were decreased in 14/14 (100%), 13/14 (93%), and 12/14 (86%) patients, respectively. PET/DTI improved diagnostic confidence in 10/14 (71%) patients and indicated that surgical candidacy be reassessed in 3/6 (50%) patients who had not undergone surgery. CONCLUSIONS: We demonstrate here the utility of AI mapping in detecting the EF based on brain regions showing decreased FDG-PET activity and, when coupled with DTI, could be a powerful tool for detecting EF and assessing WM integrity in MRI-negative epilepsy. PET/DTI could be used to further enhance clinical decision-making in epilepsy surgery.