Effectiveness of Multimodal imaging for the Evaluation of Retinal oedema And new vesseLs in Diabetic retinopathy (EMERALD).

INTRODUCTION: Diabetic macular oedema (DMO) and proliferative diabetic retinopathy (PDR) are the major causes of sight loss in people with diabetes. Due to the increased prevalence of diabetes, the workload related to these complications is increasing making it difficult for Hospital Eye Services (HSE) to meet demands. METHODS AND ANALYSIS: Effectiveness of Multimodal imaging for the Evaluation of Retinal oedema And new vesseLs in Diabetic retinopathy (EMERALD) is a prospective, case-referent, cross-sectional diagnostic study. It aims at determining the diagnostic performance, cost-effectiveness and acceptability of a new form of surveillance for people with stable DMO and/or PDR, which entails multimodal imaging and image review by an ophthalmic grader, using the current standard of care (evaluation of patients in clinic by an ophthalmologist) as the reference standard. If safe, cost-effective and acceptable, this pathway could help HES by freeing ophthalmologist time. The primary outcome of EMERALD is sensitivity of the new surveillance pathway in detecting active DMO/PDR. Secondary outcomes include specificity, agreement between new and the standard care pathway, positive and negative likelihood ratios, cost-effectiveness, acceptability, proportion of patients requiring subsequent full clinical assessment, unable to undergo imaging, with inadequate quality images or indeterminate findings. ETHICS AND DISSEMINATION: Ethical approval was obtained for this study from the Office for Research Ethics Committees Northern Ireland (reference 17/NI/0124). Study results will be published as a Health Technology Assessment monograph, in peer-reviewed national and international journals and presented at national/international conferences and to patient groups. TRIAL REGISTRATION NUMBER: NCT03490318 and ISRCTN:10856638.

ACC/AATS/AHA/ASE/ASNC/HRS/SCAI/SCCT/SCMR/STS 2019 Appropriate Use Criteria for Multimodality Imaging in the Assessment of Cardiac Structure and Function in Nonvalvular Heart Disease: A Report of the American College of Cardiology Appropriate Use Criteria Task Force, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and the Society of Thoracic Surgeons.

This document is the second of 2 companion appropriate use criteria (AUC) documents developed by the American College of Cardiology, American Association for Thoracic Surgery, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons. The first document1 addresses the evaluation and use of multimodality imaging in the diagnosis and management of valvular heart disease, whereas this document addresses this topic with regard to structural (nonvalvular) heart disease. While dealing with different subjects, the 2 documents do share a common structure and feature some clinical overlap. The goal of the companion AUC documents is to provide a comprehensive resource for multimodality imaging in the context of structural and valvular heart disease, encompassing multiple imaging modalities. Using standardized methodology, the clinical scenarios (indications) were developed by a diverse writing group to represent patient presentations encountered in everyday practice and included common applications and anticipated uses. Where appropriate, the scenarios were developed on the basis of the most current American College of Cardiology/American Heart Association Clinical Practice Guidelines. A separate, independent rating panel scored the 102 clinical scenarios in this document on a scale of 1 to 9. Scores of 7 to 9 indicate that a modality is considered appropriate for the clinical scenario presented. Midrange scores of 4 to 6 indicate that a modality may be appropriate for the clinical scenario, and scores of 1 to 3 indicate that a modality is considered rarely appropriate for the clinical scenario. The primary objective of the AUC is to provide a framework for the assessment of these scenarios by practices that will improve and standardize physician decision making. AUC publications reflect an ongoing effort by the American College of Cardiology to critically and systematically create, review, and categorize clinical situations in which diagnostic tests and procedures are utilized by physicians caring for patients with cardiovascular diseases. The process is based on the current understanding of the technical capabilities of the imaging modalities examined.

Reduced-dose CT protocol for the assessment of cerebral vasospasm.

INTRODUCTION: Despite the increased radiation dose, multimodal CT including noncontrast CT (NCT), CT angiography (CTA), and perfusion CT (PCT) remains a useful tool for the diagnosis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). The aim of this study was to assess the radiation dose and the image quality between a standard-dose and a reduced-dose multimodal CT protocol. METHODS: The study group consisted of 26 aSAH patients with a suspicion of DCI on clinical examination and transcranial doppler. Two different CT protocols were used: a standard-dose protocol (NCT 120 kV, 350 mAs; CTA 100 kV, 250 mAs; PCT 80 kV, 200 mAs) from August 2011 to October 2013 (n = 13) and a reduced-dose protocol (NCT 100 kV, 400 mAs; CTA 100 kV, 220 mAs; PCT 80 kV, 180 mAs) from November 2013 to May 2014 (n = 13). Dose-length product (DLP), effective dose, volume CT dose index (CTDI), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and overall image quality were determined for each examination. RESULTS: The overall image quality was judged as good or excellent in all cases. The reduced-dose protocol allowed a 15 % decrease in both the median total DLP (2438 vs 2898 mGy cm, p < 0.0001) and the effective dose as well as a significant decrease in median CTDI of 23, 31, and 10 % for NCT, CTA, and CTP, respectively. This dose reduction did not result in significant alteration of SNR (except for NCT) or CNR between groups. CONCLUSION: The present study showed that the reduced-dose multimodal CT protocol enabled a significant reduction of radiation dose without image quality impairment.

Staging and response assessment in lymphomas: the new Lugano classification.

Staging and response criteria were initially developed for Hodgkin lymphoma (HL) over 60 years ago, but not until 1999 were response criteria published for non-HL (NHL). Revisions to these criteria for both NHL and HL were published in 2007 by an international working group, incorporating PET for response assessment, and were widely adopted. After years of experience with these criteria, a workshop including representatives of most major international lymphoma cooperative groups and cancer centers was held at the 11(th) International Conference on Malignant Lymphoma (ICML) in June, 2011 to determine what changes were needed. An Imaging Task Force was created to update the relevance of existing imaging for staging, reassess the role of interim PET-CT, standardize PET-CT reporting, and to evaluate the potential prognostic value of quantitative analyses using PET and CT. A clinical task force was charged with assessing the potential of PET-CT to modify initial staging. A subsequent workshop was help at ICML-12, June 2013. Conclusions included: PET-CT should now be used to stage FDG-avid lymphomas; for others, CT will define stage. Whereas Ann Arbor classification will still be used for disease localization, patients should be treated as limited disease [I (E), II (E)], or extensive disease [III-IV (E)], directed by prognostic and risk factors. Since symptom designation A and B are frequently neither recorded nor accurate, and are not prognostic in most widely used prognostic indices for HL or the various types of NHL, these designations need only be applied to the limited clinical situations where they impact treatment decisions (e.g., stage II HL). PET-CT can replace the bone marrow biopsy (BMBx) for HL. A positive PET of bone or bone marrow is adequate to designate advanced stage in DLBCL. However, BMBx can be considered in DLBCL with no PET evidence of BM involvement, if identification of discordant histology is relevant for patient management, or if the results would alter treatment. BMBx remains recommended for staging of other histologies, primarily if it will impact therapy. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale, and included in new PET-based response criteria, but CT should be used in non-avid histologies. The definition of PD can be based on a single node, but must consider the potential for flare reactions seen early in treatment with newer targeted agents which can mimic disease progression. Routine surveillance scans are strongly discouraged, and the number of scans should be minimized in practice and in clinical trials, when not a direct study question. Hopefully, these recommendations will improve the conduct of clinical trials and patient management.

Summary of the UPICT Protocol for 18F-FDG PET/CT Imaging in Oncology Clinical Trials.

The Uniform Protocols for Imaging in Clinical Trials (UPICT) (18)F-FDG PET/CT protocol is intended to guide the performance of whole-body FDG PET/CT studies within the context of single- and multiple-center clinical trials of oncologic therapies by providing acceptable (minimum), target, and ideal standards for all phases of imaging. The aim is to minimize variability in intra- and intersubject, intra- and interplatform, interexamination, and interinstitutional primary or derived data. The goal of this condensed version of the much larger document is to make readers aware of the general content and subject area. The document has several main subjects: context of the imaging protocol within the clinical trial; site selection, qualification, and training; subject scheduling; subject preparation; imaging-related substance preparation and administration; imaging procedure; image postprocessing; image analysis; image interpretation; archiving and distribution of data; quality control; and imaging-associated risks and risk management.

11C-choline PET/CT and bladder cancer: lymph node metastasis assessment with pathological specimens as reference standard.

AIM: The aim of this study was to evaluate the potential role of C-choline-PET/CT in nodal assessment in patients with bladder cancer (BCa) using the pathological specimen as reference standard. PATIENTS AND METHODS: Fifty-nine patients with proven BCa were retrospectively enrolled from April 2011 to January 2014 (mean [SD] age, 70.1 [9] years; range 49-85 years). Of 59 patients, 39 (staging group) were referred to C-choline-PET/CT for preoperative lymph node (LN) evaluation before radical cystectomy and extended pelvic LN dissection. Of the 59 patients, 29 (restaging group) had C-choline-PET/CT for suspected BCa relapse after primary radical surgery. In both groups, C-choline-PET/CT findings were correlated with histology. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated to assess C-choline-PET/CT feasibility in LN assessment. Age, TNM, histology, and previous chemotherapy were analyzed as additional predictive factors. RESULTS: C-choline-PET/CT overall detection rate was 62.7% (37/59 patients). On a regional-based analysis, C-choline-PET/CT was considered positive for primary cancer and/or local relapse in bladder bed in 54.2% of the patients (32/59). Pathological LN uptake was reported in 23.7% of the patients (14/59) and systemic choline deposit (bone or lung) in 11.8% of the patients (7/59). Considering LN metastasis detection, compared with histological analysis, C-choline-PET/CT showed in the whole population a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 59%, 90%, 71%, 84%, and 81%, respectively. No other investigated factors reached statistical significance. CONCLUSIONS: C-choline-PET/CT may provide additional diagnostic information in preoperative nodal staging of patients with BCa and be considered a useful tool to restage patients with BCa suspected of relapse. Further studies are needed to assess if C-choline-PET/CT could have an influence on survival of patients with BCa.

Clinical interpretation standards and quality assurance for the multicenter PET/CT trial rubidium-ARMI.

UNLABELLED: Rubidium-ARMI ((82)Rb as an Alternative Radiopharmaceutical for Myocardial Imaging) is a multicenter trial to evaluate the accuracy, outcomes, and cost-effectiveness of low-dose (82)Rb perfusion imaging using 3-dimensional (3D) PET/CT technology. Standardized imaging protocols are essential to ensure consistent interpretation. METHODS: Cardiac phantom qualifying scans were obtained at 7 recruiting centers. Low-dose (10 MBq/kg) rest and pharmacologic stress (82)Rb PET scans were obtained in 25 patients at each site. Summed stress scores, summed rest scores, and summed difference scores (SSS, SRS, and SDS [respectively] = SSS-SRS) were evaluated using 17-segment visual interpretation with a discretized color map. All scans were coread at the core lab (University of Ottawa Heart Institute) to assess agreement of scoring, clinical diagnosis, and image quality. Scoring differences greater than 3 underwent a third review to improve consensus. Scoring agreement was evaluated with intraclass correlation coefficient (ICC-r), concordance of clinical interpretation, and image quality using κ coefficient and percentage agreement. Patient (99m)Tc and (201)Tl SPECT scans (n = 25) from 2 centers were analyzed similarly for comparison to (82)Rb. RESULTS: Qualifying scores of SSS = 2, SDS = 2, were achieved uniformly at all imaging sites on 9 different 3D PET/CT scanners. Patient scores showed good agreement between core and recruiting sites: ICC-r = 0.92, 0.77 for SSS, SDS. Eighty-five and eighty-seven percent of SSS and SDS scores, respectively, had site-core differences of 3 or less. After consensus review, scoring agreement improved to ICC-r = 0.97, 0.96 for SSS, SDS (P < 0.05). The agreement of normal versus abnormal (SSS ≥ 4) and nonischemic versus ischemic (SDS ≥ 2) studies was excellent: ICC-r = 0.90 and 0.88. Overall interpretation showed excellent agreement, with a κ = 0.94. Image quality was perceived differently by the site versus core reviewers (90% vs. 76% good or better; P < 0.05). By comparison, scoring agreement of the SPECT scans was ICC-r = 0.82, 0.72 for SSS, SDS. Seventy-six and eighty-eight percent of SSS and SDS scores, respectively, had site-core differences of 3 or less. Consensus review again improved scoring agreement to ICC-r = 0.97, 0.90 for SSS, SDS (P < 0.05). CONCLUSION: (82)Rb myocardial perfusion imaging protocols were implemented with highly repeatable interpretation in centers using 3D PET/CT technology, through an effective standardization and quality assurance program. Site scoring of (82)Rb PET myocardial perfusion imaging scans was found to be in good agreement with core lab standards, suggesting that the data from these centers may be combined for analysis of the rubidium-ARMI endpoints.

Multimodal assessment of optokinetic visual stimulation response in migraine with aura.

OBJECTIVE: This study aimed to assess activation patterns and the hemodynamic response to optokinetic stimulation in migraine with aura patients compared with controls. BACKGROUND: It has been proposed that altered visual motion processing in striate and extrastriate visual areas is present in migraine patients and might play a role in the pathophysiology of the disease. Besides activating a large visual network, optokinetic stimulation in particular has been shown to provoke symptoms associated with migraine. METHODS: In this study, we examined the response to visual stimulation in 18 migraine with aura patients compared with 18 healthy controls by using functional magnetic resonance imaging and functional transcranial Doppler, thereby assessing the activation pattern of the visual areas (V1-V5) as well as the vasomotor reactivity of the posterior cerebral artery. For stimulation, we used a vertically rotating optokinetic drum with complex colored figures. RESULTS: Group analysis of migraineurs with aura vs controls revealed different activation patterns in functional magnetic resonance imaging: attenuation of the physiological right lateralization with a significantly increased activation in the left V5 complex, the left area V3, and the right V5 complex. Analysis of the visually evoked flow response of the cerebral blood flow velocity in the posterior cerebral artery showed a larger side-difference of the offset latency (P < .05) and a reduced steepness of the decreasing slope on the left side (P < .05). CONCLUSION: Combining examinations with a good structural (functional magnetic resonance imaging) and temporal (functional transcranial Doppler) resolution is a novel approach to migraine pathophysiology. Our findings of an altered pattern of activation by optokinetic visual stimulation with hyperresponsiveness in visual areas activated by motion perception (V5 and V3) further strengthen the concept of an interictal motion-processing deficit in migraine. This is complemented by the slower restitution of the visually evoked flow response after stimulus offset in migraine with aura patients.

Comparison of software programs for the assessment of left ventricular ejection fraction using 99mTc-tetrofosmin-gated SPECT/CT: correlation with equilibrium radionuclide ventriculography in the Indian population.

OBJECTIVE: The goal of this study was to compare Emory Cardiac Toolbox (ECTb), quantitative gated SPECT (QGS), four-dimensional single photon emission computed tomography (4D-MSPECT) and Myometrix cardiac software programs for the assessment of left ventricular ejection fraction (LVEF) using 99mTc-tetrofosmin-gated SPECT/CT [myocardial perfusion SPECT (MPS)] and correlate them with the LVEF values derived from equilibrium radionuclide ventriculography (ERNV) in patients with known/suspected coronary artery disease (CAD). MATERIALS AND METHODS: A total of 109 patients (80 men, 29 women) were recruited into the study. Fifty-five patients had known CAD and 54 were referred with suspicion of CAD. All the patients underwent ERNV and MPS as per the standard protocol. ERNV was processed using the vendor-provided 'EF analysis' and gated MPS was processed using individual software programs. RESULTS: The mean LVEF on ERNV was 47.9 ± 15.5%. The mean LVEF values for ECTb, QGS, 4D-MSPECT and Myometrix were 51.5 ± 19.6, 51.0 ± 18.6, 57.1 ± 19.3 and 49.7 ± 19%, respectively. On correlation analysis, a very strong positive correlation was observed between LVEF values derived by ERNV and those derived by the MPS software programs: ECTb (r=0.842, P<0.0001), QGS (r=0.835, P<0.0001), 4D-MSPECT (r=0.830, P<0.0001) and Myometrix (r=0.875, P<0.0001). Significant correlation was also seen for LVEFs among the four software programs. Normal cutoff values for ejection fraction on ECTb, QGS, 4D-MSPECT and Myometrix were 56, 52, 54 and 51%, respectively, using a 50% or more cutoff value on ERNV. CONCLUSION: A strong correlation was observed among ECTb, QGS, 4D-MSPECT and Myometrix software programs when compared with ERNV and also between them for assessment of LVEF. However, there are subtle differences in the objective values of ejection fraction generated by individual software, which must be taken into account for clinical studies.

Engineering and performance (NEMA and animal) of a lower-cost higher-resolution animal PET/CT scanner using photomultiplier-quadrant-sharing detectors.

UNLABELLED: The dedicated murine PET (MuPET) scanner is a high-resolution, high-sensitivity, and low-cost preclinical PET camera designed and manufactured at our laboratory. In this article, we report its performance according to the NU 4-2008 standards of the National Electrical Manufacturers Association (NEMA). We also report the results of additional phantom and mouse studies. METHODS: The MuPET scanner, which is integrated with a CT camera, is based on the photomultiplier-quadrant-sharing concept and comprises 180 blocks of 13 × 13 lutetium yttrium oxyorthosilicate crystals (1.24 × 1.4 × 9.5 mm(3)) and 210 low-cost 19-mm photomultipliers. The camera has 78 detector rings, with an 11.6-cm axial field of view and a ring diameter of 16.6 cm. We measured the energy resolution, scatter fraction, sensitivity, spatial resolution, and counting rate performance of the scanner. In addition, we scanned the NEMA image-quality phantom, Micro Deluxe and Ultra-Micro Hot Spot phantoms, and 2 healthy mice. RESULTS: The system average energy resolution was 14% at 511 keV. The average spatial resolution at the center of the field of view was about 1.2 mm, improving to 0.8 mm and remaining below 1.2 mm in the central 6-cm field of view when a resolution-recovery method was used. The absolute sensitivity of the camera was 6.38% for an energy window of 350-650 keV and a coincidence timing window of 3.4 ns. The system scatter fraction was 11.9% for the NEMA mouselike phantom and 28% for the ratlike phantom. The maximum noise-equivalent counting rate was 1,100 at 57 MBq for the mouselike phantom and 352 kcps at 65 MBq for the ratlike phantom. The 1-mm fillable rod was clearly observable using the NEMA image-quality phantom. The images of the Ultra-Micro Hot Spot phantom also showed the 1-mm hot rods. In the mouse studies, both the left and right ventricle walls were clearly observable, as were the Harderian glands. CONCLUSION: The MuPET camera has excellent resolution, sensitivity, counting rate, and imaging performance. The data show it is a powerful scanner for preclinical animal study and pharmaceutical development.

[Combining CT and scintigraphy: SPECT-CT and PET-CT]. / CT combineren met scintigrafie: SPECT-CT en PET-CT.

In recent years tomographic hybrid scanners have been quickly introduced in nuclear medicine: single-photon emission computed tomography (SPECT)-CT and positron emission tomography (PET)-CT.- Both SPECT-CT and PET-CT techniques provide a higher diagnostic accuracy than conventional (non-tomographic, non-hybrid) bone scintigraphy (bone scan).- Differences between 99mTc hydroxymethylene diphosphonate (HDP) SPECT-CT or 99mTc methylene diphosphonate (MDP) SPECT-CT and 18F-fluoride PET-CT bone scanning relate to image quality, technique, availability, quantification possibilities, radiation dosimetry and financial cost.- Indications for these techniques will especially lie in the field of more accurate detection of skeletal metastases than with bone scans, patients with unexplained musculoskeletal pain, the diagnostic stage after conventional X-ray and/or MRI, and quantification of bone metabolism.

Qualitative and quantitative assessment of metal artifacts arising from implantable cardiac pacing devices in oncological PET/CT studies: a phantom study.

PURPOSE: We evaluate the magnitude of metallic artifacts caused by various implantable cardiac pacing devices (without leads) on both attenuation maps (µ-maps) and positron emission tomography (PET) images using experimental phantom studies. We also assess the efficacy of a metal artifact reduction (MAR) algorithm along with the severity of artifacts in the presence of misalignment between µ-maps and PET images. METHODS: Four pacing devices including two pacemakers (pacemakers 1 and 2) and two cardiac resynchronization therapy (CRT) devices of pacemaker (CRT-P) and defibrillator (CRT-D) type were placed in three phantoms including a cylindrical Ge-68 phantom, a water-bath phantom and an anthropomorphic heart/thorax phantom. The µ-maps were derived from computed tomography (CT) images reconstructed using the standard method supplied by the manufacturer and those reconstructed using the MAR algorithm. In addition, the standard reconstructed CT images of the last two phantoms were manually misaligned by 10 mm along the patient's axis to simulate misalignment between CT and PET images. RESULTS: The least and severest artifacts produced on both µ-maps and PET images of the Ge-68 phantom were induced by CRT-P and pacemaker 1 devices, respectively. In the water-bath phantom, CRT-P induced 17.5% over- and 9.2% underestimation of tracer uptake whereas pacemaker 1 induced 69.6% over- and 65.7% underestimation. In the heart/thorax phantom representing a pacemaker-bearing patient, pacemaker 1 induced 41.8% increase and 36.6% decrease in tracer uptake and attenuation coefficients on average in regions corresponding to bright and dark streak artifacts, respectively. Statistical analysis revealed that the MAR algorithm was successful in reducing bright streak artifacts, yet unsuccessful for dark ones. In the heart/thorax phantom, the MAR algorithm reduced the overestimations to 4.4% and the underestimations to 35.5% on average. Misalignment between µ-maps and PET images increased the peak of pseudo-uptake by approximately 20%. CONCLUSIONS: This study demonstrated that, depending on their elemental composition, different implantable cardiac pacing devices result in varying magnitudes of metal artifacts and thus pseudo-uptake on PET images. The MAR algorithm was not successful in compensating for underestimations which calls for a more efficient algorithm. The results showed that misalignments between PET and CT images render metal-related pseudo-uptake more severe.