Current barriers and recommendations on the diagnosis of transthyretin amyloid cardiomyopathy: a Delphi study.

Objectives: This study has been conducted to investigate the non-invasive diagnostic journey of patients with a transthyretin amyloid cardiomyopathy (aTTR-CM) in Turkey, identify the challenges and uncertainties encountered on the path to diagnosis from the perspectives of expert physicians, and develop recommendations that can be applied in such cases. Methods: This study employed a three-round modified Delphi method and included 10 cardiologists and five nuclear medicine specialists. Two hematologists also shared their expert opinions on the survey results related to hematological tests during a final face-to-face discussion. A consensus was reached when 80% or more of the panel members marked the "agree/strongly agree" or "disagree/strongly disagree" option. Results: The panelists unanimously agreed that the aTTR-CM diagnosis could be established through scintigraphy (using either 99mTc-PYP, 99mTc-DPD, or 99mTc-HMPD) in a patient with suspected cardiac amyloidosis (CA) without a further investigation if AL amyloidosis is ruled out (by sFLC, SPIE and UPIE). In addition, scintigraphy imaging performed by SPECT or SPECT-CT should reveal a myocardial uptake of Grade ≥2 with a heart-to-contralateral (H/CL) ratio of ≥1.5. The cardiology panelists recommended using cardiovascular magnetic resonance (CMR) and a detailed echocardiographic scoring as a last resort before considering an endomyocardial biopsy in patients with suspected CA whose scintigraphy results were discordant/inconclusive or negative but still carried a high clinical suspicion of aTTR-CM. Conclusion: The diagnostic approach for aTTR-CM should be customized based on the availability of diagnostic tools/methods in each expert clinic to achieve a timely and definitive diagnosis.

Value of volumetric and textural analysis in predicting the treatment response in patients with locally advanced rectal cancer.

OBJECTIVE: The aim of this study was to assess the value of baseline 18F-FDG PET/CT in predicting the response to neoadjuvant chemo-radiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC) via the volumetric and texture data obtained from 18F-FDG PET/CT images. METHODS:  In total, 110 patients who had undergone NCRT after initial PET/CT and followed by surgical resection were included in this study. Patients were divided into two groups randomly as a train set (n: 88) and test set (n: 22). Pathological response using three-point tumor regression grade (TRG) and metastatic lymph nodes in PET/CT images were determined. TRG1 were accepted as responders and TRG2-3 as non-responders. Region of interest for the primary tumors was drawn and volumetric features (metabolic tumor volume (MTV) and total lesion glycolysis (TLG)) and texture features were calculated. In train set, the relationship between these features and TRG was investigated with Mann-Whitney U test. Receiver operating curve analysis was performed for features with p < 0.05. Correlation between features were evaluated with Spearman correlation test, features with correlation coefficient < 0.8 were evaluated with the logistic regression analysis for creating a model. The model obtained was tested with a test set that has not been used in modeling before. RESULTS:  In train set 32 (36.4%) patients were responders. The rate of visually detected metastatic lymph node at baseline PET/CT was higher in non-responders than responders (71.4% and 46.9%, respectively, p = 0.022). There was a statistically significant difference between TLG, MTV, SHAPE_compacity, NGLDMcoarseness, GLRLM_GLNU, GLRLM_RLNU, GLZLM_LZHGE and GLZLM_GLNU between responders and non-responders. MTV and NGLDMcoarseness demonstrated the most significance (p = 0.011). A multivariate logistic regression analysis that included MTV, coarseness, GLZLM_LZHGE and lymph node metastasis was performed. Multivariate analysis demonstrated MTV and lymph node metastasis were the most meaningful parameters. The model's AUC was calculated as 0.714 (p = 0.001,0.606-0.822, 95% CI). In test set, AUC was determined 0.838 (p = 0.008,0.671-1.000, 95% CI) in discriminating non-responders. CONCLUSIONS: Although there were points where textural features were found to be significant, multivariate analysis revealed no diagnostic superiority over MTV in predicting treatment response. In this study, it was thought higher MTV value and metastatic lymph nodes in PET/CT images could be a predictor of low treatment response in patients with LARC.

18F-FDG, 68Ga-DOTATATE and 68Ga-PSMA Positive Metastatic Large Cell Neuroendocrine Prostate Tumor.

Prostate large cell neuroendocrine tumor is a rare disease. In this case, metastatic areas showing FDG uptake, somatostatin receptor positivity, and PSMA expression are shown in F-FDG PET/CT, Ga-DOTATATE PET/CT, and Ga-PSMA PET/CT in a 70-year-old man with the diagnosis of prostate large cell neuroendocrine carcinoma.

Prevalence and Localization of Hibernating Myocardium Among Patients with Left Ventricular Dysfunction.

OBJECTIVE: This study evaluated how much of the myocardium was hibernating in patients with left ventricle dysfunction and/or comorbidities who planned to undergo either surgical or interventional revascularization. Furthermore, this study also identified which irrigation areas of the coronary arteries presented more scar and hibernating tissue. METHODS: At rest, Tc-99m MIBI SPECT and cardiac F-18 FDG PET/CT images collected between March 2009 and September 2016 from 65 patients (55 men, 10 women, mean age 64±12) were retrospectively analyzed in order to evaluate myocardial viability. The areas with perfusion defects that were considered metabolic were accepted as hibernating myocardium, whereas areas with perfusion defects that were considered non-metabolic were accepted as scar tissue. RESULTS: Perfusion defects were observed in 26% of myocardium, on average 48% were associated with hibernation whereas other 52% were scar tissue. In the remaining Tc-99m MIBI images, perfusion defects were observed in the following areas in the left anterior descending artery (LAD; 31%), in the right coronary artery (RCA; 23%) and in the Left Circumflex Artery (LCx; 19%) irrigation areas. Hibernation areas were localized within the LAD (46%), LCx (54%), and RCA (64%) irrigation areas. Scar tissue was also localized within the LAD (54%), LCx (46%), and RCA (36%) irrigation areas. CONCLUSION: Perfusion defects are thought to be the result of half hibernating tissue and half scar tissue. The majority of perfusion defects was observed in the LAD irrigation area, whereas hibernation was most often observed in the RCA irrigation area. The scar tissue development was more common in the LAD irrigation zone.

Machine learning for differentiating metastatic and completely responded sclerotic bone lesion in prostate cancer: a retrospective radiomics study.

OBJECTIVE: Using CT texture analysis and machine learning methods, this study aims to distinguish the lesions imaged via 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT as metastatic and completely responded in patients with known bone metastasis and who were previously treated. METHODS: We retrospectively reviewed the 68Ga-PSMA PET/CT images of 75 patients after treatment, who were previously diagnosed with prostate cancer and had known bone metastasis. A texture analysis was performed on the metastatic lesions showing PSMA expression and completely responded sclerotic lesions without PSMA expression through CT images. Textural features were compared in two groups. Thus, the distinction of metastasis/completely responded lesions and the most effective parameters in this issue were determined by using various methods [decision tree, discriminant analysis, support vector machine (SVM), k-nearest neighbor (KNN), ensemble classifier] in machine learning. RESULTS: In 28 of the 35 texture analysis findings, there was a statistically significant difference between the two groups. The Weighted KNN method had the highest accuracy and area under the curve, has been chosen as the best model. The weighted KNN algorithm was succeeded to differentiate sclerotic lesion from metastasis or completely responded lesions with 0.76 area under the curve. GLZLM_SZHGE and histogram-based kurtosis were found to be the most important parameters in differentiating metastatic and completely responded sclerotic lesions. CONCLUSIONS: Metastatic lesions and completely responded sclerosis areas in CT images, as determined by 68Ga-PSMA PET, could be distinguished with good accuracy using texture analysis and machine learning (Weighted KNN algorithm) in prostate cancer. ADVANCES IN KNOWLEDGE: Our findings suggest that, with the use of newly emerging software, CT imaging can contribute to identifying the metastatic lesions in prostate cancer.

Technetium-99m HMPAO brain SPECT in autistic children and their families.

The purpose of the study was to investigate perfusion patterns in autistic children (AC) and their families. Ten AC (9 boys, 1 girl; mean age: 6.9+/-1.7 years) with autistic disorder defined by DSM-III-R criteria, five age-matched children (3 boys, 2 girls) as a control group, and the immediate family members of eight AC (8 mothers, 8 fathers, 7 siblings; mean ages: 39+/-4 years, 36+/-5 years and 13+/-5 years, respectively) were included in the study. Age- and sex-matched control groups for both the parents and the siblings were also included in the study. Brain perfusion images were obtained 1 h after the intravenous injection of an adjusted dose of Tc-99m HMPAO to children and the adults. Visual and semiquantitative evaluations were performed. Hypoperfusion was seen in the right posterior parietal cortex in three AC, in bilateral parietal cortex in one AC, bilateral frontal cortex in two AC, left parietal and temporal cortex in one AC, and right parietal and temporal cortex in one AC. Asymmetric perfusion was observed in the caudate nucleus in four AC. In semiquantitative analyses, statistically significant hypoperfusion was found in the right inferior and superior frontal, left superior frontal, right parietal, right mesial temporal and right caudate nucleus. In parents of AC, significant hypoperfusion was noted in the right parietal and bilateral inferior frontal cortex. In siblings of AC, perfusion in the right frontal cortex, right nucleus caudate and left parietal cortex was significantly decreased. This preliminary study suggests the existence of regional brain perfusion alterations in frontal, temporal, and parietal cortex and in caudate nucleus in AC and in their first-degree family members.

Genetic imaging study with [Tc-99m] TRODAT-1 SPECT in adolescents with ADHD using OROS-methylphenidate.

AIM: To examine theeffects on the brain of 2-month treatment withamethylphenidate extended-release formulation (OROS-MPH) using [Tc-99m] TRODAT-1SPECT in a sample of treatment-naïve adolescents with Attention Deficit/Hyperactivity Disorder (ADHD). In addition, to assess whether risk alleles (homozygosity for 10-repeat allele at the DAT1 gene were associated with alterations in striatal DAT availability. METHODS: Twenty adolescents with ADHD underwent brain single-photon emission computed tomography (SPECT) scans with [Tc-99m] TRODAT-1 at baseline and two months after starting OROS-MPH treatment with dosages up to 1 mg/kg/day. Severity of illness was estimated using the Clinical Global Impression Scale (CGI-S) and DuPaul ADHD Rating Scale-Clinician version (ARS) before treatment,1 month and 2 months after initiating OROS-MPH treatment. RESULTS: Decreased DAT availability was found in both the right caudate (pretreatment DAT binding: 224.76 ±â€¯33.77, post-treatment DAT binding: 208.86 ±â€¯28.75, p = 0.02) and right putamen (pre-treatment DAT binding: 314.41 ±â€¯55.24, post-treatment DAT binding: 285.66 ±â€¯39.20, p = 0.05) in adolescents with ADHD receiving OROS-MPH treatment. Adolescents with ADHD who showed a robust response to OROS-MPH (n = 7) had significantly greater reduction of DAT density in the right putamen than adolescents who showed less robust response to OROS-MPH (n = 13) (p = 0.02). However, between-group differences by treatment responses were not related with DAT density in the right caudate. Risk alleles (homozygosity for the 10-repeat allele of DAT1 gene) in the DAT1 gene were not associated with alterations in striatal DAT availability. CONCLUSION: Two months of OROS-MPH treatment decreased DAT availability in both the right caudate and putamen. Adolescents with ADHD who showed a robust response to OROS-MPH had greater reduction of DAT density in the right putamen. However,our findings did not support an association between homozygosity for a 10-repeat allele in the DAT1 gene and DAT density, assessedusing[Tc-99m] TRODAT-1SPECT.

Retro-orbital, Breast, Cardiac, Skin, and Subcutaneous Metastases of Neuroendocrine Tumor From a Tail Gut Cyst on 68Ga-DOTATATE PET/CT Imaging.

Tail gut cysts are rare congenital lesions developing from postanal primitive gut remnants. They are mostly benign but carry a potential of malignant transformation, such as adenocarcinoma, neuroendocrine tumor, adenosquamous carcinoma, and pseudomyxoma peritonei. We present a 39-year-old woman with a neuroendocrine tumor arising within a tail gut cyst. She underwent complete resection in 2011. After 4 years, she was admitted with breast nodules, left proptosis, and gaze difficulties. Ga-DOTATATE PET/CT demonstrated extensive metastases including pelvic, lymph node, adrenal gland, bone, retro-orbital, cardiac, breast, skin, and subcutaneous metastases.

Effects of long-term methylphenidate treatment: a pilot follow-up clinical and SPECT study.

BACKGROUND: Although abnormalities in the regional cerebral blood flow (rCBF) responses to methylphenidate (MPH) treatment have been reported in children with attention deficit hyperactivity disorder (ADHD), there are few prospective longitudinal studies assessing the long-term effects of MPH and discontinuation effects after chronic treatment. METHODS: The authors studied ten drug-naive children (2 girls, 8 boys, mean age+/-S.D.=9.60+/-1.96) diagnosed with ADHD by the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnostic criteria, using (99m)Tc-HMPAO-single photon emission computed tomography (SPECT). Patients were studied at baseline (visit 1), after 2 months of MPH treatment (visit 2) and after a drug-free period of 2 months following 12 months of MPH treatment (visit 3) at doses of 1 mg/kg/day. We evaluated SPECT data visually and semi-quantitatively. RESULTS: Two months of chronic MPH treatment resulted in visually detectable improvement in hypoperfusion in the right frontal cortex and all areas of temporal cortex with the exception of left lateral temporal cortex. This improvement was still detectable on visual evaluations of SPECT data after 2 months of treatment discontinuation. The treatment effects that were detected visually were not statistically significant in semi-quantitative analyses. CONCLUSIONS: Treatment effects of chronic MPH treatment may persist long after the discontinuation of the treatment.

Improvement in Tc-99m HMPAO brain SPECT findings during donepezil therapy in a patient with pure akinesia.

A 58-year-old man presented with a history of disturbance in initiating gait. His history revealed meningoencephalitis five years prior to admission. Neurological examination included gait disturbance as difficulty in initiation and a hesitating speech with many freezing episodes and micrographia Magnetic resonance imaging (MRI) showed diffuse hyperintensity of frontal subcortical white matter on T2 weighted images. He was diagnosed with PA. L-Dopa up to the dosages of 1000 mg/ day and selegiline 10 mg/day were given. First brain SPECT using technetium-99m labeled D,L-hexamethylpropylene amine oxime (Tc-99m HMPAO) was performed when he was taking L-dopa and selegiline. In visual evaluation, hypoperfusion in bilateral frontoparietal cortex was seen (Fig. 2). Treatment with L-dopa and selegiline produced no benefit. Donepezil 10 mg/day was begun. This therapy regimen resulted in dramatic clinical improvement within several days that was confirmed by blinded raters who watched the patient's video recordings. During this response second brain perfusion SPECT study was repeated during donepezil therapy. Markedly increased perfusion in bilateral frontoparietal cortex was observed. This is the first case of PA to develop possibly after an episode of bacterial pneumococcal meningoencephalitis and who responded to donepezil as documented by changes in clinical findings and Tc-99m HMPAO brain SPECT studies.

Atomoxetine treatment may decrease striatal dopaminergic transporter availability after 8 weeks: pilot SPECT report of three cases.

Attention deficit/hyperactivity disorder is one of the most common neurodevelopmental disorders. The pathophysiology is thought to involve noradrenaline and dopamine. The role of dopamine transporter (DAT) was evaluated in imaging studies using mostly dopamine reuptake inhibitors. Atomoxetine is a selective noradrenaline reuptake inhibitor. Here we report the results of a pilot study conducted to evaluate changes in striatal DAT after 8 weeks of atomoxetine treatment. Our results suggest that 8 weeks of atomoxetine treatment may change striatal DAT bioavailability as measured via SPECT but that change was not correlated with genotype or clinical improvement.

Water-pipe smoking effects on pulmonary permeability using technetium-99m DTPA inhalation scintigraphy.

OBJECTIVE: Although extensive work has been done on cigarette smoking and its effects on pulmonary function, there are limited number of studies on water-pipe smoking. The effects of water-pipe smoking on health are not widely investigated. The aim of this study was to determine the effects of water-pipe smoking on pulmonary permeability. METHODS: Technetium-99m DTPA inhalation scintigraphy was performed on 14 water-pipe smoker volunteers (all men, mean age 53.7 +/- 9.8) and 11 passive smoker volunteers (1 woman, 10 men, mean age 43.8 +/- 12). Clearance half-time (T 1/2) was calculated by placing a monoexponential fit on the time activity curves. Penetration index (PI) of the radioaerosol was also calculated. RESULTS: PI was 0.58 +/- 0.14 and 0.50 +/- 0.12 for water-pipe smokers (WPS) and passive smokers (PS) respectively. T 1/2 of peripheral lung was 57.3 +/- 12.7 and 64.6 +/- 13.2 min, central airways was 55.8 +/- 23.5 and 80.1 +/- 35.2 min for WPS and PS, respectively (p < or = 0.05). FEV1/FVC% was 82.1 +/- 8.5 (%) and 87.7 +/- 6.5 (%) for WPS and PS, respectively (0.025 < p < or = 0.05). CONCLUSIONS: We suggest that water-pipe smoking effects pulmonary epithelial permeability more than passive smoking. Increased central mucociliary clearance in water-pipe smoking may be due to preserved humidity of the airway tracts.

Technetium-99m HMPAO brain SPECT in children with attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a developmental, neurobehavioral syndrome with an onset in childhood. The aim of this study was to investigate the existence of regional perfusion changes in ADHD by means of Tc-99m HMPAO brain SPECT. Thirteen children with a diagnosis of ADHD and 7 healthy, age-matched controls were included in this study. Hypoperfusion was observed on the right temporal cortex in 9, and on the left temporal cortex in 3 children. The distribution of the lesions showed right lateral temporal cortex involvement in 3, right medial temporal cortex in 9 and left medial temporal cortex in 8 children. Asymmetric perfusion was seen on the caudate nucleus in 4, on the thalamus in 3 and on the frontal cortex in 6 children. There was a significant difference between children with ADHD and controls in right medial temporal cortex: cerebellum and right lateral temporal cortex: cerebellum ratios. Hypoperfusion in the right medial temporal cortex was significantly and inversely correlated with Du Paul teachers' questionnaire rating scale (r = -0.71, p = 0.006). It has been postulated that difficulty in self regulating response to stimuli in ADHD is mediated by underfunctioning of the orbital frontal cortex and subsequent connection to the limbic system. Decreased temporal cortex perfusion may dysfunction of the limbic system or the orbito-frontal-limbic axis.

Tc-99m-HMPAO uptake by bronchoalveolar cells.

Lung uptake of intravenously injected Tc-99m-HMPAO is observed in smokers and in lung toxicity due to various agents. We investigated the Tc-99m-HMPAO uptake of bronchoalveolar lavage (BAL) cells in the lungs after incubation in in vitro conditions (6 patients), intravenous injection (IV) (7 patients) and inhalation (INH) (6 patients) of Tc-99m-HMPAO in order to show whether BAL cells are also responsible for Tc-99m-HMPAO uptake in the lungs. Cell/supernatant (C/S) count ratio was 7.0 +/- 3.5, 29.3 +/- 40.8 and 8.4 +/- 4.5 for in vitro, IV and INH groups, respectively. C/Sin vitro showed a positive correlation with % alveolar macrophages (r = 0.943, p = 0.0048) and a negative correlation with % neutrophils (r = -0.945, p = 0.0045). Cells/whole BAL fluid ratio correlated with the amount of daily cigarette consumption in INH group (r = 0.95, p = 0.0037). Tc-99m-HMPAO showed adherence to mucus after inhalation. Tc-99m-HMPAO diffuses into alveolar spaces after injection and is present in BAL fluid and BAL cells both after injection and inhalation. Glutathione concentration and oxido-reductive state of the epithelial lining fluid and BAL cells may influence the lung uptake of Tc-99m-HMPAO.

Interobserver and intraobserver agreement in parathyroid scintigraphy: How can parathyroid scintigraphy be made more reliable?

OBJECTIVE: To determine the intraobserver and interobserver agreement levels in the evaluation of technetium Tc 99m sestamibi parathyroid scintigraphic images. METHODS: Ninety-eight patients with hyperparathyroidism were included in the study, and their parathyroid images were evaluated by 4 experienced nuclear medicine observers. The 98 cases were evaluated twice by each observer within an interval of 2 weeks. The evaluations were performed directly on workstations with use of digital images. A questionnaire was completed by each observer. The presence of a lesion, the number and the localizations of the lesions, and whether the lesion was clear or doubtful were all evaluated. Cohen kappa statistics and total agreement percentages were calculated by using SPSS version 11.0 software. RESULTS: The 4 observers performed 8 different evaluations and identified a minimum of 38 and a maximum of 43 cases with a parathyroid lesion (or lesions). Both the intraobserver and the interobserver agreements were "very good" for the presence of a parathyroid lesion. The intra-observer agreement was also "very good" and the interobserver agreement was "good" (for only 1 pair of observers) or "very good" for the evaluation of the number of parathyroid lesions. The intraobserver agreement was "very good" or "good" and the interobserver agreement was "good" for the lesion localization and for the presence of a doubtful lesion. CONCLUSION: Parathyroid scintigraphy seems to be an observer independent method in the detection of a parathyroid lesion, in the determination of the number of lesions, and in the localizations of the lesions. The measured high agreement between observers increases the reliability of parathyroid scintigraphy.