Differential diagnosis of parkinsonian syndromes: a comparison of clinical and automated - metabolic brain patterns' based approach.

PURPOSE: Differentiation among parkinsonian syndromes may be clinically challenging, especially at early disease stages. In this study, we used 18F-FDG-PET brain imaging combined with an automated image classification algorithm to classify parkinsonian patients as Parkinson's disease (PD) or as an atypical parkinsonian syndrome (APS) at the time when the clinical diagnosis was still uncertain. In addition to validating the algorithm, we assessed its utility in a "real-life" clinical setting. METHODS: One hundred thirty-seven parkinsonian patients with uncertain clinical diagnosis underwent 18F-FDG-PET and were classified using an automated image-based algorithm. For 66 patients in cohort A, the algorithm-based diagnoses were compared with their final clinical diagnoses, which were the gold standard for cohort A and were made 2.2 ± 1.1 years (mean ± SD) later by a movement disorder specialist. Seventy-one patients in cohort B were diagnosed by general neurologists, not strictly following diagnostic criteria, 2.5 ± 1.6 years after imaging. The clinical diagnoses were compared with the algorithm-based ones, which were considered the gold standard for cohort B. RESULTS: Image-based automated classification of cohort A resulted in 86.0% sensitivity, 92.3% specificity, 97.4% positive predictive value (PPV), and 66.7% negative predictive value (NPV) for PD, and 84.6% sensitivity, 97.7% specificity, 91.7% PPV, and 95.5% NPV for APS. In cohort B, general neurologists achieved 94.7% sensitivity, 83.3% specificity, 81.8% PPV, and 95.2% NPV for PD, while 88.2%, 76.9%, 71.4%, and 90.9% for APS. CONCLUSION: The image-based algorithm had a high specificity and the predictive values in classifying patients before a final clinical diagnosis was reached by a specialist. Our data suggest that it may improve the diagnostic accuracy by 10-15% in PD and 20% in APS when a movement disorder specialist is not easily available.

Metabolic Correlates of Dopaminergic Loss in Dementia with Lewy Bodies.

BACKGROUND: Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by 123 I-Ioflupane brain single-photon emission computed tomography of dopamine transporter and 18 F-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. OBJECTIVE: We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. METHODS: We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. RESULTS: There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. CONCLUSIONS: Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. © 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Abnormal metabolic brain network associated with Parkinson's disease: replication on a new European sample.

PURPOSE: The purpose of this study was to identify the specific metabolic brain pattern characteristic for Parkinson's disease (PD): Parkinson's disease-related pattern (PDRP), using network analysis of [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) brain images in a cohort of Slovenian PD patients. METHODS: Twenty PD patients (age 70.1 ± 7.8 years, Movement Disorder Society Unified Parkinson's Disease Motor Rating Scale (MDS-UPDRS-III) 38.3 ± 12.2; disease duration 4.3 ± 4.1 years) and 20 age-matched normal controls (NCs) underwent FDG-PET brain imaging. An automatic voxel-based scaled subprofile model/principal component analysis (SSM/PCA) was applied to these scans for PDRP-Slovenia identification. RESULTS: The pattern was characterized by relative hypermetabolism in pallidum, putamen, thalamus, brain stem, and cerebellum associated with hypometabolism in sensorimotor cortex, posterior parietal, occipital, and frontal cortices. The expression of PDRP-Slovenia discriminated PD patients from NCs (p < 0.0001) and correlated positively with patients' clinical score (MDS-UPDRS-III, p = 0.03). Additionally, its topography agrees well with the original PDRP (p < 0.001) identified in American cohort of PD patients. We validated the PDRP-Slovenia expression on additional FDG-PET scans of 20 PD patients, 20 NCs, and 25 patients with atypical parkinsonism (AP). We confirmed that the expression of PDRP-Slovenia manifests good diagnostic accuracy with specificity and sensitivity of 85-90% at optimal pattern expression cutoff for discrimination of PD patients and NCs and is not expressed in AP. CONCLUSION: PDRP-Slovenia proves to be a robust and reproducible functional imaging biomarker independent of patient population. It accurately differentiates PD patients from NCs and AP and correlates well with the clinical measure of PD progression.

Thyroid lesions incidentally detected by (18)F-FDG PET-CT - a two centre retrospective study.

BACKGROUND: Incidental (18)F-FDG uptake in the thyroid on PET-CT examinations represents a diagnostic challenge. The maximal standardized uptake value (SUVmax) is one possible parameter that can help in distinguishing between benign and malignant thyroid PET lesions. PATIENTS AND METHODS: We retrospectively evaluated (18)F-FDG PET-CT examinations of 5,911 patients performed at two different medical centres from 2010 to 2011. If pathologically increased activity was accidentally detected in the thyroid, the SUVmax of the thyroid lesion was calculated. Patients with incidental (18)F-FDG uptake in the thyroid were instructed to visit a thyroidologist, who performed further investigation including fine needle aspiration cytology (FNAC) if needed. Lesions deemed suspicious after FNAC were referred for surgery. RESULTS: Incidental (18)F-FDG uptake in the thyroid was found in 3.89% - in 230 out of 5,911 patients investigated on PET-CT. Malignant thyroid lesions (represented with focal thyroid uptake) were detected in 10 of 66 patients (in 15.2%). In the first medical centre the SUVmax of 36 benign lesions was 5.6 ± 2.8 compared to 15.8 ± 9.2 of 5 malignant lesions (p < 0.001). In the second centre the SUVmax of 20 benign lesions was 3.7 ± 2.2 compared to 5.1 ± 2.3 of 5 malignant lesions (p = 0.217). All 29 further investigated diffuse thyroid lesions were benign. CONCLUSIONS: Incidental (18)F-FDG uptake in the thyroid was found in 3.89% of patients who had a PET-CT examination. Only focal thyroid uptake represented a malignant lesion in our study - in 15.2% of all focal thyroid lesions. SUVmax should only serve as one of several parameters that alert the clinician on the possibility of thyroid malignancy.

Lung scintigraphy in the diagnosis of pulmonary embolism: current methods and interpretation criteria in clinical practice.

BACKGROUND: In current clinical practice lung scintigraphy is mainly used to exclude pulmonary embolism (PE). Modified diagnostic criteria for planar lung scintigraphy are considered, as newer scitigraphic methods, especially single photon emission computed tomography (SPECT) are becoming more popular. PATIENTS AND METHODS: Data of 98 outpatients who underwent planar ventilation/perfusion (V/Q) scintigraphy and 49 outpatients who underwent V/Q SPECT from the emergency department (ED) were retrospectively collected. Planar V/Q images were interpreted according to 0.5 segment mismatch criteria and revised PIOPED II criteria and perfusion scans according to PISA-PED criteria. V/Q SPECT images were interpreted according to the criteria suggested in EANM guidelines. Final diagnosis of PE was based on the clinical decision of an attending physician and evaluation of a 12 months follow-up period. RESULTS: Using 0.5 segment mismatch criteria and revised PIOPED II, planar V/Q scans were diagnostic in 93% and 84% of cases, respectively. Among the diagnostic planar scans readings specificity for 0.5 segment mismatch criteria was 98%, and 99% for revised PIOPED II criteria. V/Q SPECT showed a sensitivity of 100% and a specificity of 98%, without any non-diagnostic cases. In patients with low pretest probability for PE, planar V/Q scans assessed by 0.5 segment mismatch criteria were diagnostic in 92%, and in 85% using revised PIOPED II criteria, while perfusion scintigraphy without ventilation scans was diagnostic in 80%. CONCLUSIONS: Lung scintigraphy yielded diagnostically definitive results and is reliable in ruling out PE in patients from ED. V/Q SPECT has excellent specificity and sensitivity without any non-diagnostic results. Percentage of non-diagnostic results in planar lung scintigraphy is considerably smaller when 0.5 segment mismatch criteria instead of revised PIOPED II criteria are used. Diagnostic value of perfusion scintigraphy according to PISA-PED criteria is inferior to combined V/Q scintigraphy; the difference is evident especially in patients with low pretest probability for PE.

Reproducibility of 99mTc-mercaptoacetyltriglycine renography: population comparison.

PURPOSE: To evaluate reproducibility of diuretic renography, performed according to current guidelines in adult and pediatric patient populations. MATERIALS AND METHODS: Fifty adult and 50 pediatric renograms were processed twice by each of three observers. For differential renal function (DRF) assessment, intraclass correlation coefficient (ICC), standard deviation of DRF calculation and the repeatability parameter were calculated. For drainage assessment, ICC was calculated. Intraobserver and interobserver analysis was performed for both parameters. Patient groups and subgroups (age, DRF asymmetry, drainage) were compared by analysis of variance. RESULTS: Interobserver analysis, adult patient group: DRF-repeatability 4.20%, ICC 0.99. Drainage-ICC 0.92/1.00 (left/right kidney). Pediatric patient group: DRF-repeatability 7.80%, ICC 0.97. Drainage-ICC 0.93/0.85 (left/right kidney). Intraobserver analysis, adult patient group: DRF-repeatability 2.61%, ICC 0.99. Drainage-ICC 0.92/1.00 (left/right kidney). Pediatric patient group: DRF-repeatability 4.76%, ICC 0.98. Drainage-ICC 0.92/0.88 (left/right kidney). Highest repeatability and thus highest DRF dispersion was found in the subgroup of patients with poor/impaired kidney drainage and reduced DRF (repeatability 11.3%, analysis of variance, P<0.001). CONCLUSION: Reproducibility of DRF estimation was excellent in adults in both intraobserver and interobserver analysis. In pediatric patients, intraobserver DRF reproducibility was very good, whereas variation in interobserver analysis was rather high with a potential influence on patient management, but occurred mainly in a subgroup of patients with impaired drainage and ipsilaterally reduced DRF. Drainage assessment was highly reproducible in both patient groups; factors confounding drainage interpretation in discordant patient cases remained unidentified.

Radiation exposure of hemophiliacs after radiosynoviorthesis with 186Re colloid.

UNLABELLED: Very limited data are available in the literature on the doses of unwanted radiation that patients receive following treatment with radiosynoviorthesis (RSO). OBJECTIVE: The aim of this study was to assess the radiation exposure after RSO with (186)Re colloid in hemophiliacs. METHODS: This study involved 12 hemophiliacs who were treated for hemophilic joint disease with 14 RSOs by using (186)Re colloid. Whole-body scintigrams were performed 1, 6, and 24 hours and 3 and 7 days after RSO. Measurements, using a whole-body counter, were done immediately after scintigraphy, with the treated joint protected with a lead shield. The cumulative activity of (186)Re in the body and in the lymph nodes was calculated. The distribution of (186)Re in the body was determined by using the values for small colloids as proposed by the International Commission on Radiological Protection (ICRP) Publication 53. The computer code, OLINDA/EXM (Vanderbilt University, Nashville, TN), was used for the calculation of the internal dose. A constant distance of 1 m between the ankle joint and body organs, and of 0.33 m between the elbow or shoulder joint and body organs, was used to calculate the contribution of gamma radiation to the effective radiation dose. RESULTS: The mean effective dose received by hemophiliacs after RSO with (186)Re colloid was 28 +/- 9 microSv/MBq of the activity injected into the joint. The patients received 0.8-3.7 mSv (1.9 +/- 0.8 mSv) owing to the leakage of (186)Re from the treated joint and its retention in the body. The highest doses were established in the spleen (26.0 +/- 10.7 mGy), the liver (17.6 +/- 7.2 mGy), and red marrow (3.0 +/- 0.8 mGy). The contribution of gamma radiation to the effective dose was less than 0.1 mSv in RSO of the ankle, 0.4 mSv in the elbow, and 0.6 mSv in the shoulder-joint treatment. The activity of (186)Re in the regional lymph nodes was noted in 4 of the 14 treatments. In these cases, the estimated average dose received by individual lymph nodes was 14.7 +/- 1.9 Gy. CONCLUSIONS: RSO with (186)Re colloid is a safe treatment method. The effective dose received by patients after RSO by using (186)Re colloid is low, as are the radiation doses to the most exposed organs. If (186)Re is retained in the regional lymph nodes, the lymph node radiation dose would be high.

The effect of 18F-FDG-PET image reconstruction algorithms on the expression of characteristic metabolic brain network in Parkinson's disease.

PURPOSE: To evaluate the reproducibility of the expression of Parkinson's Disease Related Pattern (PDRP) across multiple sets of 18F-FDG-PET brain images reconstructed with different reconstruction algorithms. METHODS: 18F-FDG-PET brain imaging was performed in two independent cohorts of Parkinson's disease (PD) patients and normal controls (NC). Slovenian cohort (20 PD patients, 20 NC) was scanned with Siemens Biograph mCT camera and reconstructed using FBP, FBP+TOF, OSEM, OSEM+TOF, OSEM+PSF and OSEM+PSF+TOF. American Cohort (20 PD patients, 7 NC) was scanned with GE Advance camera and reconstructed using 3DRP, FORE-FBP and FORE-Iterative. Expressions of two previously-validated PDRP patterns (PDRP-Slovenia and PDRP-USA) were calculated. We compared the ability of PDRP to discriminate PD patients from NC, differences and correlation between the corresponding subject scores and ROC analysis results across the different reconstruction algorithms. RESULTS: The expression of PDRP-Slovenia and PDRP-USA networks was significantly elevated in PD patients compared to NC (p<0.0001), regardless of reconstruction algorithms. PDRP expression strongly correlated between all studied algorithms and the reference algorithm (r⩾0.993, p<0.0001). Average differences in the PDRP expression among different algorithms varied within 0.73 and 0.08 of the reference value for PDRP-Slovenia and PDRP-USA, respectively. ROC analysis confirmed high similarity in sensitivity, specificity and AUC among all studied reconstruction algorithms. CONCLUSIONS: These results show that the expression of PDRP is reproducible across a variety of reconstruction algorithms of 18F-FDG-PET brain images. PDRP is capable of providing a robust metabolic biomarker of PD for multicenter 18F-FDG-PET images acquired in the context of differential diagnosis or clinical trials.

Intercalated chemotherapy and erlotinib for non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutations.

Among attempts to delay development of resistance to tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) with activating mutations of epidermal growth factor receptor (EGFR), intercalated therapy has not been properly evaluated. In a phase II trial, 38 patients with EGFR mutated NSCLC in advanced stage were treated with 4 to 6 3-weekly cycles of intercalated schedule with gemcitabine (1250 mg/m2, days 1 and 4), cisplatin (75 mg/m2, day 2) and erlotinib (150 mg, days 5 - 15), followed by continuous erlotinib as maintenance. In addition to standard radiologic evaluation according to RECIST, PET/CT was done prior to treatment and at 6 months, using PERCIST as a method for assessment of response. The primary endpoint was progression-free survival (PFS). In general, tolerance to treatment was good, even among 8 patients with performance status 2-3 and 13 patients with brain metastases; grade 4 toxicity included 2 cases of neutropenia and 4 thrombo-embolic events. Complete response (CR) or partial response (PR) were seen in 15 (39.5%) and 17 (44.7%) cases, respectively. All cases of CR were confirmed also by PET/CT. Median PFS was 23.4 months and median overall survival (OS) was 38.3  months. After a median follow-up of 35 months, 8 patients are still in CR and on maintenance erlotinib. In conclusion, intercalated treatment for treatment-naive patients with EGFR activating mutations leads to excellent response rate and prolonged PFS and survival. Comparison of the intercalated schedule to monotherapy with TKIs in a randomized trial is warranted.

Radiosynoviorthesis for treatment of hemophilic hemarthrosis--Slovenian experience.

UNLABELLED: Radiosynoviorthesis is a well-accepted method for the treatment of recurrent hemarthrosis in hemophilic patients. OBJECTIVES: The aims of our study were to evaluate the effectiveness of radiosynoviorthesis in patients suffering from hemophilic hemarthrosis, to determine the effect of treatment on antihemophilic factor consumption, and to assess the patient's satisfaction with radiosynoviorthesis. METHODS: Between 2001 and 2003, 26 radiosynoviortheses were done in 21 hemophilic patients; in 4 patients the treatment was repeated, and in 1 patient two joints were treated. 90Y colloid was used for the knee joint, and 186Re colloid was used for ankle, shoulder, and elbow radiosynoviorthesis. RESULTS: The bleeding frequency decreased by at least 50% in 53% of patients in the year after radiosynoviorthesis, as compared to the year prior to the therapy. Considering only those patients who had at least 12 bleedings into the treated joints in the year preceding the therapy, the bleeding frequency decreased by at least 50% in 62% of these patients. In this group, the consumption of the antihemophilic factor was notably reduced (on average, by 25,800 I.U./year). All patients reported that the treated joint was much better or better than before the radiosynoviorthesis. CONCLUSION: Radiosynoviorthesis is an effective method for the treatment of hemophilic hemarthrosis, particularly in patients with frequent intra-articular bleedings. The antihemophilic factor consumption was markedly reduced only in patients with frequent joint bleeding. Radiosynoviorthesis is well accepted by patients suffering from hemophilic hemarthrosis.

Early effects of treatment on regional cerebral blood flow in first episode schizophrenia patients evaluated with 99Tc-ECD-SPECT.

OBJECTIVES: Altered regional cerebral blood flow (r-CBF) is mentioned as one of possible etiological factors or as a consequence of schizophrenia. Perfusion scintigraphic brain studies with SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) can detect areas of the brain with altered perfusion during the disease. Conflicting data exist on follow-up after treatment. The aim of our study was to evaluate r-CBF in acute first-episode schizophrenia and early effect of antipsychotic drugs on r-CBF. DESIGN AND SETTING: Clinical criteria for schizophrenia were met according to International Classification of Diseases-10th Edition (ICD-10). Psychic status and severity of the disease in each patient were evaluated with psychiatric interview, Positive and Negative Syndrome Scale (PANSS) and Clinical Global Impression (CGI) on the same day as the scintigraphic study. Brain perfusion SPECT was performed 20 minutes after 99mTc-ECD application. R-CBF was measured in 9 first-episode schizophrenic male patients 2-7 (median 6) days after the beginning of antipsychotic treatment and 8-15 (median 9) weeks later. Semiquantitative analysis of r-CBF was performed with cerebellum as the reference region. R-CBF was evaluated for 12 regions in each study. RESULTS: Decrease in perfusion in comparison to cerebellum was detected in left (90%) and right (93%) frontal lobes. Increase in perfusion between the first (t1) and the second (t2) investigation was significant (p<0.05) for both frontal regions (left 94%, right 97%). Significant decrease in PANSS (p<0.05) and CGI (p<0.001) scores was noted and correlated well with the increase of r-CBF. CONCLUSIONS: Our findings implicate that patients with first-episode schizophrenia have significant left hypoperfusion relative to the right in dorsolateral frontal lobes. Increased blood flow was observed bilaterally in dorsolateral frontal lobes after 10 weeks of antipsychotic medication. Significant amelioration of r-CBF correlated with clinical improvement.

Nonischemic ST segment elevation in hypertrophic cardiomyopathy due to chest wall deformity from kyphoscoliosis.

A 57-year-old male was admitted with suspected acute coronary syndrome. He reported experiencing moderate chest pain when walking during the day prior to admission, but had very prominent ST segment elevations in the precordial electrocardiography (EKG) leads. A physical examination revealed remarkable severe kyphoscoliosis with chest deformity. The patient's cardiac troponin levels remained normal, while cardiac ultrasound and magnetic resonance imaging of the chest confirmed hypertrophic cardiomyopathy (HCM) with severe thickening of the interventricular septum. Ischemic heart disease was ruled out by myocardial perfusion imaging with (99m)Tc-MIBI during rest and dipyridamole-induced stress without showing irreversible or reversible myocardial ischemia. Our diagnosis was that the chest pain was noncardiac in origin and that the pronounced ST segment elevations in the precordial EKG leads reflected the severely hypertrophic interventricular septum through the normally thick left ventricular free wall. The patient's chest wall deformity brought his septum and the ventricular free wall nearly parallel to the left side of the chest wall, allowing for complete expression of the reciprocal EKG pattern of septal hypertrophy. We suggest that EKG findings should always be interpreted with the chest wall shape being kept in mind.