Towards the OR of the future: introducing an adaptive and technology-embracing OR wing layout.

PURPOSE: Overageing and climate change cause a need for making processes in the operating room wing (OR wing) more efficient. While many promising technologies are available today, traditional OR wings are not designed for seamlessly integrating these aids. To overcome this discrepancy, we present and motivate multiple ideas on how to transform current architectural design strategies. METHODS: The presented concepts originate from expert discussions and studies of the available literature, but also from experiences made in the course of daily care delivery. Additionally, a comprehensive evaluation of current and historic OR theatre designs and the problems which are encountered herein has been conducted. RESULTS: We present three innovative concepts regarding the restructuring of traditional OR wing layouts. To achieve better process optimization, hygiene, and energy efficiency, we propose to divide the OR wing into separate "patient", "procedure" and "staff" zones. For better flexibility regarding perioperative needs and technology integration, we propose to use a hexagon shape combined with reconfigurable walls for designing operating rooms. CONCLUSION: The concepts presented herein provide a solid foundation for further considerations regarding perioperative process optimization and seamless integration of technology into modern OR wing facilities. We aim at expanding on these results to develop a comprehensive vision for the OR wing of the future.

The hospital of the future: rethinking architectural design to enable new patient-centered treatment concepts.

PURPOSE: Today's hospitals are designed as collections of individual departments, with limited communication and collaboration between medical sub-specialties. Patients are constantly being moved between different places, which is detrimental for patient experience, overall efficiency and capacity. Instead, we argue that care should be brought to the patient, not vice versa, and thus propose a novel hospital architecture concept that we refer to as Patient Hub. It envisions a truly patient-centered, department-less facility, in which all critical functions occur in the same building and on the same floor. METHODS: To demonstrate the feasibility and benefits of our concept, we selected an exemplary patient scenario and used 3D software to simulate resulting workflows for both the Patient Hub and a traditional hospital based on a generic hospital template by Kaiser-Permanente. RESULTS: According to our workflow simulations, the Patient Hub model effectively eliminates waiting and transfer times, drastically simplifies wayfinding, reduces overall traveling distances by 54%, reduces elevator runs by 78% and improves access to quality views from 67 to 100% for patient rooms, from 0 to 100% for exam rooms and from 0 to 38% for corridors. In addition, the interaction of related medical fields is improved while maintaining the quality of care and the relationship between patients and caregivers. CONCLUSION: With the Patient Hub concept, we aim at rethinking traditional hospital layouts. We were able to demonstrate, alas on a proof-of-concept basis, that it is indeed feasible to place the patient at the very center of operations, while increasing overall efficiency and capacity at the same time and maintaining the quality of care.

A multicentric IT platform for storage and sharing of imaging-based radiation dosimetric data.

PURPOSE: The MEDIRAD project is about the effects of low radiation dose in the context of medical procedures. The goal of the work is to develop an informatics service that will provide the researchers of the MEDIRAD project with a platform to share acquired images, along with the associated dosimetric data pertaining to the radiation resulting from the procedure. METHODS: The authors designed a system architecture to manage image data and dosimetric data in an integrated way. DICOM and non-DICOM data are stored in separated repositories, and the link between the two is provided through a semantic database, i.e., a database whose information schema in aligned with an ontology. RESULTS: The system currently supports CT, PET, SPECT, and NM images as well as dose reports. Currently, two workflows for non-DICOM data generated from dosimetric calculations have been taken into account, one concerning Monte Carlo-based calculation of organ doses in Chest CT, and the other estimation of doses in nontarget organs in 131I targeted radionuclide therapy of the thyroid. CONCLUSION: The system is currently deployed, thus providing access to image and related dosimetric data to all MEDIRAD users. The software was designed in such a way that it can be reused to support similar needs in other projects.

Higher availability of α4ß2 nicotinic receptors (nAChRs) in dorsal ACC is linked to more efficient interference control.

Nicotinic acetylcholine receptors (nAChRs) are widely distributed in the human brain and play an important role in the neuromodulation of brain networks implicated in attentional processes. Previous work in humans showed that heteromeric α4ß2 nAChRs are abundant in the cingulo-insular network underlying attentional control. It has been proposed that cholinergic neuromodulation by α4ß2 nAChRs is involved in attentional control during demanding tasks, when additional resources are needed to minimize interference from task-irrelevant stimuli and focus on task-relevant stimuli. Here we investigate the link between the availability of α4ß2 nAChRs in the cingulo-insular network and behavioral measures of interference control using two versions of the Stroop paradigm, a task known to recruit cingulo-insular areas. We used a previously published PET dataset acquired in 24 non-smoking male subjects in the context of a larger study which investigated the brain distribution of nAChRs in two clinical groups using 2-[(18)F]F-A-85380 PET. We found that higher availability of α4ß2 nAChRs in the dorsal anterior cingulate cortex (ACC) predicted better interference control independently of group and age. In line with animal models, our results support the view that the availability of α4ß2 nAChRs in the dorsal ACC is linked with more efficient attentional control.

Integrating radiomics into holomics for personalised oncology: from algorithms to bedside.

Radiomics, artificial intelligence, and deep learning figure amongst recent buzzwords in current medical imaging research and technological development. Analysis of medical big data in assessment and follow-up of personalised treatments has also become a major research topic in the area of precision medicine. In this review, current research trends in radiomics are analysed, from handcrafted radiomics feature extraction and statistical analysis to deep learning. Radiomics algorithms now include genomics and immunomics data to improve patient stratification and prediction of treatment response. Several applications have already shown conclusive results demonstrating the potential of including other "omics" data to existing imaging features. We also discuss further challenges of data harmonisation and management infrastructure to shed a light on the much-needed integration of radiomics and all other "omics" into clinical workflows. In particular, we point to the emerging paradigm shift in the implementation of big data infrastructures to facilitate databanks growth, data extraction and the development of expert software tools. Secured access, sharing, and integration of all health data, called "holomics", will accelerate the revolution of personalised medicine and oncology as well as expand the role of imaging specialists.

A semantic database for integrated management of image and dosimetric data in low radiation dose research in medical imaging.

Medical ionizing radiation procedures and especially medical imaging are a non negligible source of exposure to patients. Whereas the biological effects of high absorbed doses are relatively well known, the effects of low absorbed doses are still debated. This work presents the development of a computer platform called Image and Radiation Dose BioBank (IRDBB) to manage research data produced in the context of the MEDIRAD project, a European project focusing on research on low doses in the context of medical procedures. More precisely, the paper describes a semantic database linking dosimetric data (such as absorbed doses to organs) to the images corresponding to X-rays exposure (such as CT images) or scintigraphic images (such as SPECT or PET images) that allow measuring the distribution of a radiopharmaceutical. The main contributions of this work are: 1) the implementation of the semantic database of the IRDBB system and 2) an ontology called OntoMEDIRAD covering the domain of discourse involved in MEDIRAD research data, especially many concepts from the DICOM standard modelled according to a realist approach.

A Comparison of Two Statistical Mapping Tools for Automated Brain FDG-PET Analysis in Predicting Conversion to Alzheimer's Disease in Subjects with Mild Cognitive Impairment.

OBJECTIVE: Automated voxel-based analysis methods are used to detect cortical hypometabolism typical of Alzheimer's Disease (AD) on FDG-PET brain scans. We compared the accuracy of two clinically validated tools for their ability to identify those MCI subjects progressing to AD at followup, to evaluate the impact of the analysis method on FDG-PET diagnostic performance. METHODS: SPMGrid and BRASS (Hermes Medical Solutions, Stockholm, Sweden) were tested on 131 MCI and elderly healthy controls from the EADC PET dataset. The concordance between the tools was tested by correlating the quantitative parameters (z- and t-values), calculated by the two software tools, and by measuring the topographical overlap of the abnormal regions (Dice score). Three independent expert readers blindly assigned a diagnosis based on the two map sets. We used conversion to AD dementia as the gold standard. RESULTS: The t-map and z-map calculated with SPMGrid and BRASS, respectively, showed a good correlation (R > .50) for the majority of individual cases (128/131) and for the majority of selected regions of interest (ROIs) (98/116). The overlap of the hypometabolic patterns from the two tools was, however, poor (Dice score .36). The diagnostic performance was comparable, with BRASS showing significantly higher sensitivity (.82 versus .59) and SPMGrid showing higher specificity (.87 versus .52). CONCLUSION: Despite similar diagnostic performance in predicting conversion to AD in MCI subjects, the two tools showed significant differences, and the maps provided by the tools showed limited overlap. These results underline the urgency for standardization across FDG-PET analysis methods for their use in clinical practice.

Nicotinic Acetylcholine Receptor Density in the "Higher-Order" Thalamus Projecting to the Prefrontal Cortex in Humans: a PET Study.

PURPOSE: The parcellation of the thalamus into different nuclei involved in different corticothalamocortical loops reflects its functional diversity. The connections between the mediodorsal nucleus and the prefrontal cortex play a major role in cognition, particularly in the rapid processing of behaviorally relevant information. The thalamus is the brain region with the highest density in α4ß2 nicotinic acetylcholine receptors, the main human nicotinic acetylcholine receptor subtype. The aim of this study was to investigate the possible role of the nicotinic cholinergic system in the thalamo-cortical loops measuring receptor density in different subregions of the thalamus, based on their cortical connectivity. PROCEDURES: We studied α4ß2 nicotinic acetylcholine receptors using positron emission tomography and [18F]Fluoro-A-85380, a radiotracer specific for this receptor subtype, in 36 non-smoking male subjects, including 12 healthy controls and 24 patients with epilepsy. [18F]Fluoro-A-85380 ratio index of binding potential was compared by a repeated measures general linear model, including the thalamic subregions and the brain hemisphere as within-subject factor and clinical groups as between-subject factor. RESULTS: The "prefrontal" thalamus, the subregion including the mediodorsal nucleus, had a significantly higher nicotinic acetylcholine receptor density than all other thalamic subregions. These findings were confirmed when analyzing solely the 12 healthy controls. CONCLUSIONS: This particular neurochemical organization of the thalamus supports a major role of the cholinergic system in the loops between the thalamus and the prefrontal cortex. The highest nicotinic acetylcholine receptor density in the « higher-order thalamus ¼ could partly explain the beneficial effect of acute nicotine on attentional and executive functions and possibly the pathophysiology of some neuropsychiatric disorders.

Recurrent prostate cancer after radical prostatectomy: restaging performance of 18F-choline hybrid PET/MRI.

To evaluate the diagnostic performance of a whole-body 18F-choline (FCH) hybrid PET/MRI for prostate cancer patients at biochemical relapse after radical prostatectomy (RP) compared to pelvic multiparametric MRI (mpMRI), one of the standard imaging modality for this patient population. From 2010 to 2016, 58 whole-body FCH PET/MRI studies with mpMRI acquisitions were performed in 53 prostate cancer patients relapsing after curative RP. Median PSA and PSA doubling time (PSA DT) at PET study were 1.5 ng/ml and 6.5 months, respectively. The overall positivity rate of FCH PET/MRI was 58.6% (n = 34), dropping to 44% in patients with a PSA ≤ 2 ng/ml (n = 36). Median PSA values in positive and negative PET/MRI studies were 2.2 ng/ml and 0.8 ng/ml, respectively, with no differences in PSA DT (6.5 vs. 6.6 months). A PSA value ≥ 1.5 ng/ml was a significant predictor of positivity on PET/MRI studies. Compared to PET, mpMRI identified more local relapses (17 vs. 14, p = 0.453) while PET outperformed whole-body Dixon MRI for regional (16 vs. 9, p = 0.016) and distant (12 vs. 6, p = 0.031) metastases. Compared to pelvic mpMRI, the treatment approach turned out to be influenced more frequently using whole-body FCH hybrid PET/MRI studies (58.6% vs. 38%). In prostate cancer patients with biochemical recurrence after RP, whole-body FCH PET/MRI achieved a higher detection rate of nodal/distant metastases compared to pelvic mpMRI alone, increasing the change of treatment strategy by more than 20%.

Nicotinic receptor abnormalities as a biomarker in idiopathic generalized epilepsy.

PURPOSE: Mutations of cholinergic neuronal nicotinic receptors have been identified in the autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE), associated with changes on PET images using [18F]-F-85380-A (F-A-85380), an α4ß2 nicotinic receptor ligand. The aim of the present study was to evaluate potential changes in nicotinic receptor availability in other types of epilepsy. METHODS: We included 34 male participants, 12 patients with idiopathic generalized epilepsy (IGE), 10 with non-lesional diurnal focal epilepsy, and 12 age-matched healthy controls. All patients underwent PET/CT using F-A-85380 and [18F]-fluorodeoxyglucose (FDG), 3D T1 MRI and diffusion tensor imaging (DTI). F-A-85380 and FDG images were compared with the control group using a voxel-wise (SPM12) and a volumes of interest (VOI) analysis. RESULTS: In the group of patients with IGE, the voxel-wise and VOI analyses showed a significant increase of F-A-85380 ratio index of binding potential (BPRI, corresponding to the receptor availability) in the anterior cingulate cortex (ACC), without structural changes on MRI. At an individual level, F-A-85380 BPRI increase in the ACC could distinguish IGE patients from controls and from patients with focal epilepsy with good accuracy. CONCLUSIONS: We observed focal changes of density/availability of nicotinic receptors in IGE, namely an increase in the ACC. These data suggest that the modulation of α4ß2 nicotinic receptors plays a role not only in ADNFLE, but also in other genetic epileptic syndromes such as IGE and could serve as a biomarker of epilepsy syndromes with a genetic background.

Prognostic value of revascularising viable myocardium in elderly patients with stable coronary artery disease and left ventricular dysfunction: a PET/CT study.

Sparse information is available on the role of cardiac viability imaging in elderly patients. We aimed at evaluating the prognostic value of FDG-PET/CT in elderly patients with stable coronary artery disease (CAD) and reduced left ventricular ejection fraction (rLVEF) before revascularisation. Elderly patients (> 65 years old, mean 74 ± 7 years old) with CAD and rLVEF were followed after cardiac FDG-PET/CT and stratified according to presence/absence of viable myocardium and subsequent revascularisation. Fatal events of any cause as well as hospitalisations related to acute cardiac conditions were reported as clinical end-points. Predictors of fatal events in patients with viable myocardium (> 1 myocardium segment/20) were analysed. A total of 89 patients were followed (64 viable myocardia; 37 and 27 patients with and without subsequent revascularisation, respectively). The change in LVEF during follow-up (2.1 ± 1.6 years) was 3.8 ± 6.6% (P = 0.013) and - 0.75 ± 2.6% (P = 0.170) in patients with and without revascularisation, respectively. Log-rank (P = 0.037) and multivariate analysis (Wald: 6.305, P = 0.012) showed viable myocardium to be significantly associated with fatal events if not revascularised. Elderly patients with viable myocardium might potentially benefit from revascularisation procedures as improved left ventricular ejection fraction and survival were observed in our retrospective study as compared to patients in whom a revascularisation procedure was denied. Viable myocardium as detected by cardiac FDG PET/CT was associated with better clinical outcomes in elderly patients when revascularised.

Local recurrence of squamous cell carcinoma of the head and neck after radio(chemo)therapy: Diagnostic performance of FDG-PET/MRI with diffusion-weighted sequences.

PURPOSE: To determine the diagnostic performance of FDG-PET/MRI with diffusion-weighted imaging (FDG-PET/DWIMRI) for detection and local staging of head and neck squamous cell carcinoma (HNSCC) after radio(chemo)therapy. MATERIALS AND METHODS: This was a prospective study that included 74 consecutive patients with previous radio(chemo)therapy for HNSCC and in whom tumour recurrence or radiation-induced complications were suspected clinically. The patients underwent hybrid PET/MRI examinations with morphological MRI, DWI and FDG-PET. Experienced readers blinded to clinical/histopathological data evaluated images according to established diagnostic criteria taking into account the complementarity of multiparametric information. The standard of reference was histopathology with whole-organ sections and follow-up ≥24 months. Statistical analysis considered data clustering. RESULTS: The proof of diagnosis was histology in 46/74 (62.2%) patients and follow-up (mean ± SD = 34 ± 8 months) in 28/74 (37.8%). Thirty-eight patients had 43 HNSCCs and 46 patients (10 with and 36 without tumours) had 62 benign lesions/complications. Sensitivity, specificity, and positive and negative predictive value of PET/DWIMRI were 97.4%, 91.7%, 92.5% and 97.1% per patient, and 93.0%, 93.5%, 90.9%, and 95.1% per lesion, respectively. Agreement between imaging-based and pathological T-stage was excellent (kappa = 0.84, p < 0.001). CONCLUSION: FDG-PET/DWIMRI yields excellent results for detection and T-classification of HNSCC after radio(chemo)therapy. KEY POINTS: • FDG-PET/DWIMRI yields excellent results for the detection of post-radio(chemo)therapy HNSCC recurrence. • Prospective one-centre study showed excellent agreement between imaging-based and pathological T-stage. • 97.5% of positive concordant MRI, DWI and FDG-PET results correspond to recurrence. • 87% of discordant MRI, DWI and FDG-PET results correspond to benign lesions. • Multiparametric FDG-PET/DWIMRI facilitates planning of salvage surgery in the irradiated neck.

Long-term results confirmed that 18F-FDG-PET/CT was an excellent diagnostic modality for early detection of vascular grafts infection.

BACKGROUND: We sought to evaluate the potential role of positron emission tomography-computed tomography (PET-CT) for the detection and diagnosis of potential infections of vascular grafts using combining metabolic (i.e., radioactive fluorine-fluoro-D-deoxyglucose [18F-FDG]) PET with morphological (CT) information and investigate long-term capability. METHODS: Seventeen patients with suspected vascular-graft infection underwent thoracic-abdominal-pelvic FDG PET combined with contrast-enhanced CT using a hybrid PET-CT scanner providing co-registered PET and CT images. RESULTS: In this retrospect study, we suspected graft infection in 14 of 17 patients detected using PET-CT and increased the maximal uptake of 18F-FDG around the grafts. Other vascular localizations were not observed. All patients with positive PET-CT results underwent redo-surgery, and the infection was ultimately confirmed using microbiological testing in 12 of 14 patients. Follow-up time was median of 58 months (range 36-73 months) for all 17 patients. In these patients, there was no further evidence of graft infection found on clinical and imaging follow-up. CONCLUSIONS: This is first investigation presenting long-term follow-up, which confirmed that 18F-FDG-PET/CT is an excellent diagnostic modality for suspected vascular graft infection. 18F-FDG PET-CT exhibited a sensitivity of 100% and specificity of 71.4% for the detection of vascular-graft infection.

Pannexin1 links lymphatic function to lipid metabolism and atherosclerosis.

Extracellular ATP is a central signaling molecule in inflammatory responses. Pannexin1 (Panx1) channels release ATP in a controlled manner and have been implicated in various inflammatory pathologies, but their role in atherogenesis remains elusive. Using atherosclerosis-susceptible mouse models with ubiquitous deletion of Panx1 (Panx1 -/- Apoe -/- ) or with Cre recombinase-mediated deletion of Panx1 in endothelial cells and monocytes (Tie2-Cre Tg Panx1 fl/fl Apoe -/- ; Panx1 del Apoe -/- ), we identified a novel role for Panx1 in the lymphatic vasculature. Atherosclerotic lesion development in response to high-cholesterol diet was enhanced in Panx1 del Apoe -/- mice, pointing to an atheroprotective role for Panx1 in endothelial and/or monocytic cells. Unexpectedly, atherogenesis was not changed in mice with ubiquitous Panx1 deletion, but Panx1 -/- Apoe -/- mice displayed reduced body weight, serum cholesterol, triglycerides and free fatty acids, suggesting altered lipid metabolism in these Panx1-deficient mice. Mechanistically, Panx1 -/- Apoe -/- mice showed impairment of lymphatic vessel function with decreased drainage of interstitial fluids and reduced dietary fat absorption. Thus, the detrimental effect of Panx1 deletion in endothelial and/or monocytic cells during atherogenesis is counterbalanced by an opposite effect resulting from impaired lymphatic function in ubiquitous Panx1-deficient mice. Collectively, our findings unveil a pivotal role of Panx1 in linking lymphatic function to lipid metabolism and atherosclerotic plaque development.

Whole-Body SPECT/CT versus Planar Bone Scan with Targeted SPECT/CT for Metastatic Workup.

PURPOSE: The use of SPECT/CT in bone scans has been widespread in recent years, but there are no specific guidelines concerning the optimal acquisition protocol. Two strategies have been proposed: targeted SPECT/CT for equivocal lesions detected on planar images or systematic whole-body SPECT/CT. Our aim was to compare the diagnostic accuracy of the two approaches. METHODS: 212 consecutive patients with a history of cancer were referred for bone scans to detect bone metastases. Two experienced readers randomly evaluated for each patient either planar images with one-field SPECT/CT targeted on equivocal focal uptakes (targeted SPECT/CT) or a whole-body (two-field) SPECT/CT acquisition from the base of the skull to the proximal femurs (whole-body SPECT/CT). The exams were categorized as "nonmetastatic," "equivocal," or "metastatic" on both protocols. The presence or absence of any extra-axial skeletal lesions was also assessed. The sensitivity and specificity of both strategies were measured using the results of subsequent imaging follow-up as the reference standard. RESULTS: Whole-body SPECT/CT had a significantly higher sensitivity than targeted SPECT/CT to detect bone metastases (p = 0.0297) and to detect extra-axial metastases (p = 0.0266). There was no significant difference in specificity among the two approaches. CONCLUSION: Whole-body SPECT/CT is the optimal modality of choice for metastatic workup, including detection of extra-axial lesions, with improved sensitivity and similar specificity compared to targeted SPECT/CT.

Strategic roadmap for an early diagnosis of Alzheimer's disease based on biomarkers.

The diagnosis of Alzheimer's disease can be improved by the use of biological measures. Biomarkers of functional impairment, neuronal loss, and protein deposition that can be assessed by neuroimaging (ie, MRI and PET) or CSF analysis are increasingly being used to diagnose Alzheimer's disease in research studies and specialist clinical settings. However, the validation of the clinical usefulness of these biomarkers is incomplete, and that is hampering reimbursement for these tests by health insurance providers, their widespread clinical implementation, and improvements in quality of health care. We have developed a strategic five-phase roadmap to foster the clinical validation of biomarkers in Alzheimer's disease, adapted from the approach for cancer biomarkers. Sufficient evidence of analytical validity (phase 1 of a structured framework adapted from oncology) is available for all biomarkers, but their clinical validity (phases 2 and 3) and clinical utility (phases 4 and 5) are incomplete. To complete these phases, research priorities include the standardisation of the readout of these assays and thresholds for normality, the evaluation of their performance in detecting early disease, the development of diagnostic algorithms comprising combinations of biomarkers, and the development of clinical guidelines for the use of biomarkers in qualified memory clinics.

Structural Basis of Bone Fragility in Young Subjects with Inflammatory Bowel Disease: A High-resolution pQCT Study of the SWISS IBD Cohort (SIBDC).

BACKGROUND: The onset of inflammatory bowel disease (IBD) during childhood/adolescence compromises peak bone mass acquisition and predisposes to fractures later in life. However, the structural basis for bone fragility in young adults with IBD remains unknown. METHODS: One hundred two young subjects from the Swiss IBD cohort were included. Areal bone mineral density (aBMD) at distal radius, hip, and spine as well as morphometric vertebral fractures were assessed using dual-energy x-ray absorptiometry technique. Volumetric (v)BMD, trabecular, and cortical bone microstructure at the distal radius and tibia were assessed by high-resolution peripheral quantitative computed tomography. Areal, vBMD, and microstructure were compared between patients with IBD and healthy matched controls (n = 389). Multiple regression analysis was used to evaluate variables associated with bone microarchitecture and fractures. RESULTS: Clinical fractures were reported in 37 IBD subjects (mean age 23 yrs), mostly of the forearm; 5 subjects had morphometric vertebral fractures. After adjusting for age, sex, and height, tibia trabecular (Tb)vBMD, thickness, and distribution were significantly associated with fractures, whereas aBMD was not. After adjusting for aBMD, radius Tb distribution and tibia (Tb)vBMD and trabecular thickness still remained associated with fractures. Compared with healthy controls, patients with IBD had significantly lower aBMD at all sites, as well as alteration in (Tb)vBMD and trabecular microstructure at the distal radius and tibia, and these alterations were correlated with disease severity. CONCLUSIONS: Young patients with IBD have low aBMD and altered trabecular bone microarchitecture compared with healthy controls. The latter is independently associated with fractures and may predispose increased susceptibility to fragility fractures throughout life.

Downstream indication to revascularization following hybrid cardiac PET/MRI: preliminary results.

BACKGROUND: Hybrid PET/MRI allows the acquisition of both fluorine-18-fluorodeoxyglucose (F-FDG) PET and cardiac magnetic resonance (CMR) during one session. Whether this will result in different referral to coronary revascularization (CR) is unknown. We compared this new hybrid method with all-nuclear/all-CMR methods in the assessment of viable myocardium and in downstream referral to CR. PATIENTS AND METHODS: Overall, 12 patients with rest perfusion defects on a single photon emission computed tomography (SPECT) were recruited for cardiac viability assessment using a PET/MRI device. Perfusion (SPECT and CMR), metabolism, late gadolinium enhancement (LGE), and contractility were compared using a 20-segments bull's eye for agreement. The patterns of ischemia/viability were compared between all-nuclear, all-CMR, and hybrid methods. Downstream CR was proposed after correlating findings to coronary angiography. RESULTS: The SPECT and CMR perfusion denoted poor agreement [agreement rate (AR): 60%; κ: 0.191, P<0.004]. The added PET metabolism concurred in reclassifying 19.2% of segments with intermediate or unassessable LGE using the hybrid method. Overall, the all-CMR method showed better agreement with the hybrid method than the all-nuclear method for findings of normal (AR: 100%, κ: 1.00 vs. 65.8% %; κ: 0.347, respectively; P<0.001), scar (AR: 85%; κ: 0.675 vs. 80.8%; κ: 0.596, respectively; P<0.001), and ischemic segments (AR: 95.8%; κ: 0.881 vs. 75.8%; κ: 0.168, respectively; P<0.001). Downstream CR was proposed in four, 11, and 12 vessels by the all-nuclear, all-CMR, or hybrid methods, respectively. CONCLUSION: Compared with all-CMR, the hybrid method allowed the reclassification of 19.2% segments. Using CMR perfusion instead of SPECT perfusion had a significant impact on downstream target vessel revascularization.

Clinical validity of brain fluorodeoxyglucose positron emission tomography as a biomarker for Alzheimer's disease in the context of a structured 5-phase development framework.

The use of Alzheimer's disease (AD) biomarkers is supported in diagnostic criteria, but their maturity for clinical routine is still debated. Here, we evaluate brain fluorodeoxyglucose positron emission tomography (FDG PET), a measure of cerebral glucose metabolism, as a biomarker to identify clinical and prodromal AD according to the framework suggested for biomarkers in oncology, using homogenous criteria with other biomarkers addressed in parallel reviews. FDG PET has fully achieved phase 1 (rational for use) and most of phase 2 (ability to discriminate AD subjects from healthy controls or other forms of dementia) aims. Phase 3 aims (early detection ability) are partly achieved. Phase 4 studies (routine use in prodromal patients) are ongoing, and only preliminary results can be extrapolated from retrospective observations. Phase 5 studies (quantify impact and costs) have not been performed. The results of this study show that specific efforts are needed to complete phase 3 evidence, in particular comparing and combining FDG PET with other biomarkers, and to properly design phase 4 prospective studies as a basis for phase 5 evaluations.

Clinical validity of presynaptic dopaminergic imaging with 123I-ioflupane and noradrenergic imaging with 123I-MIBG in the differential diagnosis between Alzheimer's disease and dementia with Lewy bodies in the context of a structured 5-phase development framework.

The use of biomarkers (BMs) for accurate diagnosis of Alzheimer's disease (AD) has been proposed by recent diagnostic criteria; however, their maturity is not sufficient to grant implementation in the clinical routine. A proper diagnostic process requires not only confirmation of the disease but also the exclusion of similar disorders entering differential diagnosis, like dementia with Lewy bodies (DLB). This review is aimed at evaluating the clinical validity of 123I-ioflupane brain single photon emission tomography and 123I-MIBG cardiac scintigraphy as imaging BMs for DLB. For this purpose, we used an adapted version of the 5-phase oncology framework for BMs development. A review of the literature was conducted using homogenous search criteria with other BMs addressed in parallel reviews. Results of our literature search showed that the rationale for the use of both BMs in the differential diagnosis of DLB and AD is strong (phase 1) and that they allow a good discrimination ability (phase 2), but studies investigating BMs distribution antemortem and postmortem on pathology are lacking. Moreover, thresholds for test positivity have not been defined for 123I-MIBG. The 2 BMs have not been yet assessed in early phases of DLB and AD (phase 3). No phase 4 and phase 5 studies have so far been carried out. This review highlights the priorities to address in future investigations to enable the proper use of 123I-ioflupane and 123I-MIBG for the differential diagnosis of dementia.