Iron Deficiency Caused by Intestinal Iron Loss-Novel Candidate Genes for Severe Anemia.

The adult human body contains about 4 g of iron. About 1-2 mg of iron is absorbed every day, and in healthy individuals, the same amount is excreted. We describe a patient who presents with severe iron deficiency anemia with hemoglobin levels below 6 g/dL and ferritin levels below 30 ng/mL. Although red blood cell concentrates and intravenous iron have been substituted every month for years, body iron stores remain depleted. Diagnostics have included several esophago-gastro-duodenoscopies, colonoscopies, MRI of the liver, repetitive bone marrow biopsies, psychological analysis, application of radioactive iron to determine intact erythropoiesis, and measurement of iron excretion in urine and feces. Typically, gastrointestinal bleeding is a major cause of iron loss. Surprisingly, intestinal iron excretion in stool in the patient was repetitively increased, without gastrointestinal bleeding. Furthermore, whole exome sequencing was performed in the patient and additional family members to identify potential causative genetic variants that may cause intestinal iron loss. Under different inheritance models, several rare mutations were identified, two of which (in CISD1 and KRI1) are likely to be functionally relevant. Intestinal iron loss in the current form has not yet been described and is, with high probability, the cause of the severe iron deficiency anemia in this patient.

Cardiac Sympathetic Activity and Rhythm Control Following Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation-A Prospective 123I-mIBG-SPECT/CT Imaging Study.

BACKGROUND: Pulmonary vein isolation (PVI) and antiarrhythmic drug therapy are established treatment strategies to preserve sinus rhythm in atrial fibrillation (AF). However, the efficacy of both interventional and pharmaceutical therapy is still limited. Solid evidence suggests an important role of the cardiac sympathetic nervous system in AF. In this blinded, prospective observational study, we studied left ventricular cardiac sympathetic activity in patients treated with PVI and with antiarrhythmic drugs. Prospectively, Iodine-123-benzyl-guanidine single photon emission computer tomography (123I-mIBG-SPECT) was performed in a total of 23 patients with paroxysmal AF, who underwent PVI (n = 20) or received antiarrhythmic drug therapy only (n = 3), respectively. 123I-mIBG planar and SPECT/CT scans were performed before and 4 to 8 weeks after PVI (or initiation of drug therapy, respectively). For semiquantitative SPECT image analysis, attenuation-corrected early/late images were analyzed. Quantitative SPECT analysis was performed using the AHA 17-segment model of the left ventricle. RESULTS: PVI with point-by-point radiofrequency ablation led to a significantly (p < 0.05) higher visual sympathetic innervation defect score when comparing pre-and post PVI. Newly emerging innervation deficits post PVI were localized predominantly in the inferior lateral wall. These findings were corroborated by semiquantitative SPECT analysis identifying inferolateral segments with a reduced tracer uptake in comparison to SPECT before PVI. Following PVI, patients with an AF relapse showed a different sympathetic innervation pattern compared to patients with sufficient rhythm control. CONCLUSIONS: PVI results in novel defects of cardiac sympathetic innervation. Differences in cardiac sympathetic innervation remodelling following PVI suggest an important role of the cardiac autonomous nervous system in the maintenance of sinus rhythm following PVI.

Cardiac Autonomic Nervous System and Ventricular Arrhythmias: The Role of Radionuclide Molecular Imaging.

Widely established compared to myocardial perfusion imaging, cardiac autonomous nervous system (CANS) assessment by radiopharmaceutical means is of potential use especially to arrhythmogenic diseases not correlated with anatomic or functional alterations revealed by classical imaging techniques. Molecular imaging of both pre- and postsynaptic functions of the autonomous nervous system is currently feasible, since single photon emission tomography (SPECT) and positron emission tomography (PET) have the ability to reveal the insights of molecular pathophysiology depicting both sympathetic and parasympathetic imbalance in discrete heart pathologies. This review provides not only a brief presentation of radiopharmaceuticals used for non-invasive CANS imaging in the case of ventricular arrhythmias, but also a current update on ventricular tachycardias, cardiomyopathies, Brugada and Long QT syndrome literature.

Coronary artery calcium burden, carotid atherosclerotic plaque burden, and myocardial blood flow in patients with end-stage renal disease: A non-invasive imaging study combining PET/CT and 3D ultrasound.

BACKGROUND: Imaging-based measures of atherosclerosis such as coronary artery calcium score (CACS) and coronary flow reserve (CFR) as well as carotid atherosclerotic plaque burden (cPB) are predictors of cardiovascular events in the general population. The objective of this study was to correlate CACS, cPB, myocardial blood flow (MBF), and CFR in patients with end-stage renal disease (ESRD). METHODS AND RESULTS: 39 patients (mean age 53 ± 12 years) with ESRD prior to kidney transplantation were enrolled. MBF and CFR were quantified at baseline and under hyperemia by 13N-NH3-PET/CT. CACS was calculated from low-dose CT scans acquired for PET attenuation correction. cPB was assessed by 3D ultrasound. Uni- and multivariate regression analyses between these and clinical parameters were performed. Median follow-up time for clinical events was 4.4 years. Kaplan-Meier survival estimates with log-rank test were performed with regards to cardiovascular (CV) events and death of any cause. CACS and cPB were associated in ESRD patients (r = 0.48; p ≤ 0.01). While cPB correlated with age (r = 0.43; p < 0.01), CACS did not. MBFstress was negatively associated with age (r = 0.44; p < 0.01) and time on dialysis (r = 0.42; p < 0.01). There were negative correlations between MBFstress and CACS (r = - 0.62; p < 0.001) and between MBFstress and cPB (r = - 0.43; p < 0.01). Age and CACS were the strongest predictors for MBFstress. CFR was impaired (< 2.0) in eight patients who also presented with higher cPB and higher CACS compared to those with a CFR > 2.0 (p = 0.06 and p = 0.4). In contrast to MBFstress, there was neither a significant correlation between CFR and CACS (r = - 0.2; p = 0.91) nor between CFR and cPB (r = - 0.1; p = 0.55). CV event-free survival was associated with reduced CFR and MBFstress (p = 0.001 and p < 0.001) but not with cPB or CACS. CONCLUSIONS: CACS, cPB, and MBFstress are associated in patients with ESRD. Atherosclerosis is earlier detected by MBFstress than by CFR. CV event-free survival is associated with impaired CFR and MBFstress.

Initial experience with [18F]DPA-714 TSPO-PET to image inflammation in primary angiitis of the central nervous system.

PURPOSE: Primary angiitis of the central nervous system (PACNS) is a heterogeneous, rare, and poorly understood inflammatory disease. We aimed at non-invasive imaging of activated microglia/macrophages in patients with PACNS by PET-MRI targeting the translocator protein (TSPO) with [18F]DPA-714 to potentially assist differential diagnosis, therapy monitoring, and biopsy planning. METHODS: In total, nine patients with ischemic stroke and diagnosed or suspected PACNS underwent [18F]DPA-714-PET-MRI. Dynamic PET scanning was performed for 60 min after injection of 233 ± 19 MBq [18F]DPA-714, and MRI was simultaneously acquired. RESULTS: In two PACNS patients, [18F]DPA-714 uptake patterns exceeded MRI correlates of infarction, whereas uptake was confined to the infarct in four patients where initial suspicion of PACNS could not be confirmed. About three patients with PACNS or cerebral predominant lymphocytic vasculitis showed no or only faintly increased uptake. Short-term [18F]DPA-714-PET follow-up in a patient with PACNS showed reduced lesional [18F]DPA-714 uptake after anti-inflammatory treatment. Biopsy in the same patient pinpointed the source of tracer uptake to TSPO-expressing immune cells. CONCLUSIONS: [18F]DPA-714-PET imaging may facilitate the diagnosis and treatment monitoring of PACNS. Further studies are needed to fully understand the potential of TSPO-PET in deciphering the heterogeneity of the disease.

A Cardiac Metastasis of Follicular Thyroid Carcinoma With Partly Squamous Cell Differentiation: Detection in FDG-PET Preceded Visibility on Echocardiography and MRI by More Than a Year.

PET using the radiotracer F-fluorodeoxyglucose (FDG) was performed in a patient who presented with elevated thyroglobulin (Tg) levels several years after initial therapy of follicular thyroid carcinoma (oncocytic variant) and in whom high-dose radioiodine (I) failed to locate recurrent tumor or to decrease Tg levels. A focal fluorodeoxyglucose uptake in the apical septum of the heart did not have a discernible correlate in echocardiography or MRI for more than 12 months. Finally, a metastasis of the follicular thyroid carcinoma with partly squamous cell differentiation was confirmed and treated by resection and stereotactic body radiotherapy.

Diagnostic Value of Diffusion Tensor Imaging and Positron Emission Tomography in Early Stages of Frontotemporal Dementia.

BACKGROUND: Due to suboptimal sensitivity and specificity of structural and molecular neuroimaging tools, the diagnosis of behavioral variant frontotemporal dementia (bvFTD) remains challenging. OBJECTIVE: Investigation of the sensitivity of diffusion tensor imaging (DTI) and fluorodeoxyglucose positron emission tomography (FDG-PET) to detect cerebral alterations in early stages of bvFTD despite inconspicuous conventional MRI. METHODS: Thirty patients with early stages of bvFTD underwent a detailed neuropsychological examination, cerebral 3T MRI with DTI analysis, and FDG-PET. After 12 months of follow-up, all patients finally fulfilled the diagnosis of bvFTD. Individual FDG-PET data analyses showed that 20 patients exhibited a "typical" pattern for bvFTD with bifrontal and/or temporal hypometabolism (bvFTD/PET+), and that 10 patients showed a "non-typical"/normal pattern (bvFTD/PET-). DTI data were compared with 42 healthy controls in an individual and voxel-based group analysis. To examine the clinical relevance of the findings, associations between pathologically altered voxels of DTI or FDG-PET results and behavioral symptoms were estimated by linear regression analyses. RESULTS: DTI voxel-based group analyses revealed microstructural degeneration in bifrontal and bitemporal areas in bvFTD/PET+ and bvFTD/PET- groups. However, when comparing the sensitivity of individual DTI data analysis with FDG-PET, DTI appeared to be less sensitive. Neuropsychological symptoms were considerably related to neurodegeneration within frontotemporal areas identified by DTI and FDG-PET. CONCLUSION: DTI seems to be an interesting tool for detection of functionally relevant neurodegenerative alterations in early stages of bvFTD, even in bvFTD/PET- patients. However, at a single subject level, it seems to be less sensitive than FDG-PET. Thus, improvement of individual DTI analysis is necessary.

Impact of presynaptic sympathetic imbalance in long-QT syndrome by positron emission tomography.

OBJECTIVE: We investigated the impact of cardiac presynaptic norepinephrine recycling in patients with long-QT syndrome (LQTS) using positron emission tomography (PET) with 11C-meta-hydroxyephedrine ([11C]mHED-PET). METHODS: [11C]mHED-PET was performed in 25 patients with LQTS (LQT1: n=14; LQT2: n=11) and 20 healthy controls and correlated with clinical parameters. [11C]mHED-PET images were analysed for global and regional retention indices (RI) and washout rates (WO) reflecting dynamic parameters of the tracer activity. RESULTS: Global and regional RI values were similar between patients with LQTS and controls. Although the global WO rates were similar between these groups, regional WO rates were on average higher in the lateral left ventricle (LV) wall in patients with LQTS (dose, mean ±SD; 0.08±0.14 vs 0.00%±0.09% min-1; p=0.033). In addition, patients with LQTS with a longer QTc interval showed a higher global WO rate. Clinical symptoms correlated with higher global WO rates. In the presence of normal global WO rates, asymptomatic LQTS patients showed higher global RI values. CONCLUSION: The increased regional WO rate of [11C]mHED in the lateral LV suggests an imbalance of presynaptic catecholamine reuptake and release, resulting in a higher synaptic catecholamine concentration, in particular in LQT1 patients. This might enhance ß-adrenoceptor signalling and thereby aggravate inherited ion channel dysfunction and may facilitate occurrence of ventricular tachyarrhythmias. Detection of regional differences in LV sympathetic nervous function may modify disease expression and potentially serve as a non-invasive risk marker in congenital LQTS. TRIAL REGISTRATION NUMBER: 2006-002767-41;Results.

Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography for improving diagnosis of infection in patients on CF-LVAD: longing for more 'insights'.

Aim: Presence and consequent extent of infection in patients on continuous-flow left ventricular assist devices (CF-LVADs) can be challenging with the current diagnostic tools. The present study sought to demonstrate the diagnostic power of 18F-Fluorodeoxyglucose-Positron-Emission Tomography/Computed Tomography (18F-FDG PET/CT) in detecting infection in patients supported with CF-LVAD. Background: The present study sought to demonstrate the diagnostic power of 18F-fluorodeoxyglucose-positron-emission tomography/computed tomography (18F-FDG PET/CT) in detecting infection in patients supported with CF-LVAD. Methods and results: Between July 2009 and April 2016, 61 PET/CT examinations were performed in 47 patients (median age 64.13 years, IQR 18.77) supported with a CF-LVAD. PET/CT assessments were performed qualitatively and quantitatively at three different levels: at the piercing site of driveline (first level), along the intracorporeal course of driveline (second level), and around the device (third level). Final diagnosis of LVAD infection was prospectively performed and was based upon microbiological samples taken at hospital admission, during the surgical revision/transplantation and recurrence of symptoms on long-term follow-up. At last follow-up a total of 40 (65.57%) final diagnoses of LVAD-infection could be ascertained. Matching the final diagnosis with the PET/CT assessments the sensitivity, specificity, and positive and negative predictive value were 90.0, 71.4, 85.71, and 78.94%, respectively. Level sub-analyses of SUV max showed an optimal discriminator power for levels 1 and 2 (AUC of level 1-0.824, P < 0.001; AUC of level 2-0.849, P < 0.001, respectively). At the third level semi-quantitative analysis showed poor discriminator power (AUC 0.589, P = 0.33). Qualitative visual analysis instead indicated a trend toward significance (P = 0.07). Conclusions: Quantitative 18F-FDG PET/CT is an optimal diagnostic tool in detecting superficial and deep driveline infections. However, diagnostic accuracy with regard to the diagnosis of pump housing infection is limited. Here, clinical and qualitative PET/CT analyses must be better considered.

Metabolic volume performs better than SUVmax in the detection of left ventricular assist device driveline infection.

PURPOSE: A continuous-flow left ventricular assist device (LVAD) is a new and highly promising therapy in supporting end-stage heart failure patients, either bridging them to heart transplantation or as a destination therapy. Infection is one of the major complications associated with LVAD implants. 18F-FDG PET/CT has already been shown to be useful in the detection of LVAD infection. The goal of this study was to compare the diagnostic accuracy of different PET analysis techniques (visual grading versus SUVmax and metabolic volume). METHODS: We retrospectively analyzed 48 patients with implanted LVAD who underwent an 18F-FDG PET/CT that were either suspected to have a driveline or device infection or inflammation of unknown origin. PET/CT was analyzed qualitatively (visual grading) and quantitatively (SUVmax and metabolic volume) and matched to the final clinical diagnosis concerning driveline infection. The final diagnosis (standard of reference) was made at the end of clinically recorded follow-up or transplantation and included microbiological cultures of the driveline exit site and/or surgical samples, and clinical signs of infection despite negative cultures as well as recurrence of symptoms. RESULTS: Sensitivity, specificity, positive and negative predictive value were 87.5%, 79%, 81% and 86% for visual score, 87.5%, 87.5%, 87.5% and 87.5% for SUVmax and 96%, 87.5%, 88.5%, 95.5% for metabolic volume, respectively. ROC analysis revealed an AUC of .929 for SUVmax and .969 for metabolic volume. Both SUVmax and metabolic volume had a high detection rate of patients with driveline infection (21/24 = 91.5% true positive vs. 23/26 = 88.5% true positive, respectively). However, metabolic volume detected more patients without any infection correctly (1/22 = 4.5% false negative vs. 3/24 = 12.5% false negative). CONCLUSIONS: 18F-FDG PET/CT is a valuable tool for the diagnosis of LVAD driveline infection with high diagnostic accuracy. Particularly the use of the metabolic volume yields very high accuracy and performs slightly better than SUVmax.

Supporting imaging modalities for improving diagnosis of prosthesis endocarditis: preliminary results of a single-center experience with 18F-FDG-PET/CT.

BACKGROUND: The aim of the current study was to evaluate the role of PET-CT in the diagnosis of prosthetic valve endocarditis (PVE). METHODS: This is a single-center study including 13 PET/CT examinations performed between February 2009 and March 2016 in 13 patients (76.9% men, mean age 68.1 years, IQR 11.1) because of suspect of PVE. Median interval time between first operation and PET/CT examination was 19.02 months (IQR 85.5). Final diagnosis was made according to pathological criteria (histological and microbiological) of the Duke classification. RESULTS: Eleven patients (84.6%) presented at the hospital admission positive blood cultures. Eight patients (61.5%) had inconclusive transesophageal echocardiography (TEE). Abnormal 18F-FDG uptake suggestive of active PVE was observed in 10 patients (76.9%), whereas in 3 patients (23.1%) PET/CT did not show any pathological tracer uptake at the level of the previous implanted prostheses. PET/CT revealed 15 (115.4%) new extracardiac findings and one (7.7%) new cardiac focus not previously detected in TEE. All patients underwent redo surgery. Matching the intraoperative findings with those of PET/CT, a total of 10 true positives, 2 true negatives, no false positive and 1 false negative finding was reported. Sensitivity, specificity, and positive and negative predictive values of PET/CT were 90.9%, 100%, 100% and 50% whereas for TEE they were 81.82%, 50%, 81.82%, and 50% respectively. In 61.63% of patients (N. 8) PET/CT and echo findings were concordant. In those cases the diagnosis of endocarditis was confirmed in all. CONCLUSIONS: This study highlights the potential advantages of PET-CT in patients with suspected prosthesis endocarditis. Further prospective evaluations are needed to confirm those preliminary results.

Routine 18F-FDG PET/CT does not detect inflammation in the left atrium in patients with atrial fibrillation.

Increasing evidence supports a role of inflammation in the development of atrial fibrillation (AF). However, direct evidence of persistent inflammatory activity in the atria of AF patients is scarce. In this study, we used 18-Fluor-Deoxyglucose positron emission tomography computed tomography (18F-FDG PET/CT) to determine atrial inflammation in patients with and without AF. Retrospectively, 18F-FDG PET/CT scans were analyzed. 37 patients with a history of AF were compared to an age and sex matched control group with no history of AF. Standardized uptake values were obtained in the atrial walls, in the left ventricular wall, and in the right ventricular blood pool, respectively. Target to background ratios (TBR) were determined in the atrial and left ventricular walls and compared between the two groups. TBR values of the left atrial wall were slightly but not significantly higher in patients with AF (1.21 ± 0.27) compared to those without AF (1.14 ± 0.29; p = 0.85). Likewise, a weak but not significant difference was observed in signal intensities in the right atrial wall between patients in the AF (1.14 ± 0.45) and the control group (0.96 ± 0.2; p = 0.41). TBR values of the left ventricular myocardium did not differ between the groups; no significant correlation was found between the TBR in the left and right atrial wall and blood glucose levels. 18F-FDG PET/CT performed under routine conditions did not detect a significant difference in inflammatory activity in the left or right atrium between patients with and without AF. Contrary to previous reports, these results therefore do not clearly support a role for ongoing atrial inflammation in patients with AF. Prospective clinical studies using myocardial glucose uptake suppression strategies may be helpful to clarify these issues.

Evaluation of 131I scintigraphy and stimulated thyroglobulin levels in the follow up of patients with DTC: a retrospective analysis of 1420 patients.

AIM: To study the clinical yield of diagnostic whole body 131I scintigraphy (DxWBS) in the follow-up of differentiated thyroid carcinoma (DTC) patients in relation to stimulated thyroglobulin (sTg) in the initial post-ablation setting, as well as in the setting of repeated monitoring in course of further DTC follow-up. METHODS: Data of 1420 thyroidectomized and radioiodine remnant-ablated DTC patients following a well-defined therapy and standardized follow-up protocol were evaluated. DxWBS and sTg were evaluated separately and in combination for various follow-up time points. The factual administration of the recorded indication for further oncologic therapy (excluding radioiodine therapies given for minimal normal remnants) within the following 4 months after follow-up served as the standard of reference. Furthermore, DxWBS was compared to post therapy WBS and SPECT(/CT) if available. Subgroup analysis was carried out for DTC patients < 45 years old at diagnosis without distant metastasis. The diagnostic impact of cervical ultrasound was not assessed. RESULTS: sTg can identify the patients at risk better than DxWBS. Furthermore, the most sensitive time point to assess response appears to be a time point beyond 3 months after RRA. When information received from both imaging and laboratory measurements are concordant, i.e. both construe absence of remaining disease, only a small fraction of patients (<2%) required treatment in the future. The strongest effect was observed 12 months after RRA. Only 0.9% of the negative DxWBS patients with concordant sTg below the functional sensitivity at this time point required treatment thereafter. CONCLUSION: A complete omission of DxWBS in the post-RRA surveillance of DTC is justified once DxWBS is negative and sTg is below the functional sensitivity (with no evidence of thyroglobulin antibodies), as patients showing this combination of test results (especially 12 months after RRA) show an at worst marginal risk of recurrence. In all other cases DxWBS may still be justified.

Imaging matrix metalloproteinase activity in multiple sclerosis as a specific marker of leukocyte penetration of the blood-brain barrier.

The enzymes gelatinase A/matrix metalloproteinase-2 (MMP-2) and gelatinase B/MMP-9 are essential for induction of neuroinflammatory symptoms in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS); in the absence of these enzymes, the disease does not develop. We therefore investigated the cellular sources and relative contributions of MMP-2 and MMP-9 to disease at early stages of EAE induction. We demonstrated that MMP-9 from an immune cell source is required in EAE for initial infiltration of leukocytes into the central nervous system and that MMP-9 activity is a reliable marker of leukocyte penetration of the blood-brain barrier. We then developed a molecular imaging method to visualize MMP activity in the brain using fluorescent- and radioactive-labeled MMP inhibitors (MMPis) in EAE animals and used the radioactive MMP ligand for positron emission tomography (PET) imaging of MMP activity in patients with MS. In contrast to traditional T1-gadolinium contrast-enhanced MRI, MMPi-PET enabled tracking of MMP activity as a unique feature of early lesions and ongoing leukocyte infiltration. MMPi-PET therefore allows monitoring of the early steps of MS development and provides a sensitive, noninvasive means of following lesion formation and resolution in murine EAE and human MS.

[(68)Ga]DOTATATE PET/MRI and [(18)F]FDG PET/CT are complementary and superior to diffusion-weighted MR imaging for radioactive-iodine-refractory differentiated thyroid cancer.

PURPOSE: The purpose of this study was to determine whether [(68)Ga]DOTATATE PET/MRI with diffusion-weighted imaging (DWI) can replace or complement [(18)F]FDG PET/CT in patients with radioactive-iodine (RAI)-refractory differentiated thyroid cancer (DTC). METHODS: The study population comprised 12 patients with elevated thyroglobulin and a negative RAI scan after thyroidectomy and RAI remnant ablation who underwent both [(18)F]FDG PET/CT and [(68)Ga]DOTATATE PET/MRI within 8 weeks of each other. The presence of recurrent cancer was evaluated on a per-patient, per-organ and per-lesion basis. Histology, and prior and follow-up examinations served as the standard of reference. RESULTS: Recurrent or metastatic tumour was confirmed in 11 of the 12 patients. [(68)Ga]DOTATATE PET(/MRI) correctly identified the tumour burden in all 11 patients, whereas in one patient local relapse was missed by [(18)F]FDG PET/CT. In the lesion-based analysis, overall lesion detection rates were 79/85 (93 %), 69/85 (81 %) and 27/82 (33 %) for [(18)F]FDG PET/CT, [(68)Ga]DOTATATE PET/MRI and DWI, respectively. [(18)F]FDG PET(/CT) was superior to [(68)Ga]DOTATATE PET(/MRI) in the overall evaluation and in the detection of pulmonary metastases. In the detection of extrapulmonary metastases, [(68)Ga]DOTATATE PET(/MRI) showed a higher sensitivity than [(18)F]FDG PET(/CT), at the cost of lower specificity. DWI achieved only poor sensitivity and was significantly inferior to [(18)F]FDG PET in the lesion-based evaluation in the detection of both extrapulmonary and pulmonary metastases. CONCLUSION: [(18)F]FDG PET/CT was more sensitive than [(68)Ga]DOTATATE PET/MRI in the evaluation of RAI-refractory DTC, mostly because of its excellent ability to detect lung metastases. In the evaluation of extrapulmonary lesions, [(68)Ga]DOTATATE PET(/MRI) was more sensitive and [(18)F]FDG PET(/CT) more specific. Furthermore, DWI did not provide additional information and cannot replace [(18)F]FDG PET for postoperative monitoring of patients with suspected RAI-refractory DTC.

[(18)F]FDG PET/CT outperforms [(18)F]FDG PET/MRI in differentiated thyroid cancer.

PURPOSE: To evaluate the diagnostic potential of PET/MRI with [(18)F]FDG in comparison to PET/CT in patients with differentiated thyroid cancer suspected or known to have dedifferentiated. METHODS: The study included 31 thyroidectomized and remnant-ablated patients who underwent a scheduled [(18)F]FDG PET/CT scan and were then enrolled for a PET/MRI scan of the neck and thorax. The datasets (PET/CT, PET/MRI) were rated regarding lesion count, conspicuity, diameter and characterization. Standardized uptake values were determined for all [(18)F]FDG-positive lesions. Histology, cytology, and examinations before and after treatment served as the standards of reference. RESULTS: Of 26 patients with a dedifferentiated tumour burden, 25 were correctly identified by both [(18)F]FDG PET/CT and PET/MRI. Detection rates by PET/CT and PET/MRI were 97 % (113 of 116 lesions) and 85 % (99 of 113 lesions) for malignant lesions, and 100 % (48 of 48 lesions) and 77 % (37 of 48 lesions) for benign lesions, respectively. Lesion conspicuity was higher on PET/CT for both malignant and benign pulmonary lesions and in the overall rating for malignant lesions (p < 0.001). There was a difference between PET/CT and PET/MRI in overall evaluation of malignant lesions (p < 0.01) and detection of pulmonary metastases (p < 0.001). Surgical evaluation revealed three malignant lesions missed by both modalities. PET/MRI additionally failed to detect 14 pulmonary metastases and 11 benign lesions. CONCLUSION: In patients with thyroid cancer and suspected or known dedifferentiation, [(18)F]FDG PET/MRI was inferior to low-dose [(18)F]FDG PET/CT for the assessment of pulmonary status. However, for the assessment of cervical status, [(18)F]FDG PET/MRI was equal to contrast-enhanced neck [(18)F]FDG PET/CT. Therefore, [(18)F]FDG PET/MRI combined with a low-dose CT scan of the thorax may provide an imaging solution when high-quality imaging is needed and high-energy CT is undesirable or the use of a contrast agent is contraindicated.

Contributory Role of Fluorine 18-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Diagnosis and Clinical Management of Infections in Patients Supported With a Continuous-Flow Left Ventricular Assist Device.

BACKGROUND: The current study sought to demonstrate the advantages offered by fluorine 18-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) in patients supported with continuous-flow left ventricular assist devices (CF-LVADs) in detecting infection and the consequent effect on clinical decisions. METHODS: Between April 2009 and September 2013, 40 PET examinations were performed in 31 patients (78.1% men; mean age, 51.0 ± 14.9 years) supported with a CF-LVAD. In group A (19 examinations in 14 patients), PET/CT was performed to detect infectious focus in patients without external signs of driveline involvement but with at least two of the following infection signs: recurrent fever, positive blood culture, or elevated infectious indicators. In group B (21 examinations in 17 patients), PET/CT aimed to assess the internal extension of infection in patients with external signs of driveline infection. RESULTS: In 50% of the cases of the patients in group A, abnormal (18)F-FDG uptake (9 patients) was related to VAD components. Matching the results with the final diagnosis, we reported 9 true-positive, 8 true-negative, no false-negative, and 2 false-positive findings. New information unrelated to VAD was found in 9 patients (50%): pneumonia in 3, colon diverticulitis in 3, sternal dehiscence in 1, paravertebral abscess in 1, and erysipelas in 1. In group B, superficial abnormal (18)F-FDG uptake was found at the piercing site of the driveline in 2 patients, deeper extension of infection along the driveline in 10, initial involvement of the pump housing in 2, and full involvement of the device in 4. These findings contributed to changing the clinical management in 84.2% of group A patients and in 85.7% of group B patients: 16 patients were scheduled for urgent transplantation, 2 underwent surgical revision of the driveline, 7 required prolonged antibiotic therapy, and 3 underwent colonoscopy. CONCLUSIONS: This single-center experience highlights the diagnostic value of PET/CT in detecting the localization and internal extension of infection to internal VAD components. Moreover, this information notably influences the therapeutic management.

Inhomogeneous myocardial stress perfusion in SPECT studies predicts future allograft dysfunction in heart transplant recipients.

BACKGROUND: Myocardial perfusion gated single photon emission computed tomography (SPECT) can be used for non-invasive detection of coronary artery stenosis and cardiac allograft vasculopathy (CAV), which is a crucial factor for the long-term survival of heart transplant (HTx) recipients. A frequently observed finding in myocardial perfusion imaging of patients after HTx is inhomogeneous myocardial perfusion. This finding is not associated with epicardial CAV, but its prognostic relevance is unclear so far. We therefore evaluated the prognosis of patients with homogeneous versus inhomogeneous myocardial stress perfusion. METHODS: One hundred four HTx patients (mean 3.6 ± 2.9 years after HTx) without significant stress-induced ischemia (summed stress score ≤3) in gated SPECT and without CAV were included. Myocardial stress perfusion was visually assessed as homogeneous, moderately, or severely inhomogeneous. The mean follow-up period after SPECT was 9.4 ± 3.1 years. End points were the diagnosis of CAV, major cardiac events (MACE) or death, and the development of allograft dysfunction (left ventricular ejection fraction, LVEF <45 %). RESULTS: Of all HTx patients, 24 % enrolled in this study (n = 25) presented with inhomogeneous myocardial perfusion. Compared to the patients with homogeneous perfusion, these patients were at higher risk for developing allograft dysfunction (multivariate hazard ratio, HR = 5.59). As to the development of CAV, the occurrence of MACE, or death, no statistical differences were observed between patients with homogenous and inhomogeneous perfusion. There was no correlation between myocardial perfusion pattern and prior cardiac allograft rejections. CONCLUSIONS: Inhomogeneous myocardial stress perfusion in SPECT studies predicts a higher risk for future development of allograft dysfunction in HTx patients (LVEF <45 %) but is not associated with future CAV, MACE, or overall survival.

Not all DTC patients with N positive disease deserve the attribution "high risk". Contribution of the MSDS trial.

BACKGROUND AND OBJECTIVES: To investigate if patients with thyroid carcinoma having N1a disease are at the same risk with N1b using the collective of the well-defined European prospective Multicentre Study Differentiated Thyroid Cancer (MSDS). METHODS: Overall (OS) and event free survival (EFS) were calculated. Cox multivariable regression analysis was performed in order to calculate Hazard ratios (HR). RESULTS: EFS was significantly decreased only in patients with N1b metastasis as compared to N0 patients and became worse when N1a was concomitantly affected. A superior survival in favor of N1a patients as compared to N1b patients with regard to EFS was also observed. The patients having N1a disease showed no differences in the EFS as compared to N0. OS did not differ significantly in any of the groups. There was an increased HR for events with regards to histology, T-stage, tumor size, UICC stage and cervical lymph node metastasis. Tumor size showed a significantly increased risk for OS. CONCLUSIONS: Patients with pT3b and pT4a tumors with N1b are of higher risk for relapse, albeit not affecting overall survival. Patients with N1a are of no higher risk. The risk stratification of these patients may be adapted accordingly.