Long-Term Prognostic Value of Automated Measurements in Nuclear Cardiology: Comparisons with Expert Scoring.

Background and Objectives: Automated methods for the analysis of myocardial perfusion studies have been incorporated into clinical practice, but they are currently used as adjuncts to the visual interpretation. We aimed to investigate the role of automated measurements of summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) as long-term prognostic markers of morbidity and mortality, in comparison to the prognostic value of expert reading. Materials and Methods: The study was conducted at the Nuclear Medicine Laboratory of the University of Thessaly, in Larissa, Greece. A total of 378 consecutive patients with known or suspected coronary artery disease were enrolled in the study. All participants were referred to our laboratory for the performance of stress/rest myocardial perfusion single photon emission computed tomography. Automated measurements of SSS, SRS, and SDS were obtained by Emory Cardiac Toolbox (ECTb (Version 3.0), Emory University, Atlanta, GA, USA), Myovation (MYO, Xeleris version 3.05, GE Healthcare, Chicago, IL, USA), and Quantitative Perfusion SPECT (QPS (Version 4.0), Cedars-Sinai Medical Center, Los Angeles, CA, USA) software packages. Follow-up data were recorded after phone contacts, as well as through review of hospital records. Results: Expert scoring of SSS and SDS had significantly greater prognostic ability in comparison to all software packages (p < 0.001 for all comparisons). Similarly, ECTb-obtained SRS measurements had significantly lower prognostic ability in comparison to expert scoring (p < 0.001), while expert scoring of SRS showed significantly higher prognostic ability compared to MYO (p = 0.018) and QPS (p < 0.001). Conclusions: Despite the useful contribution of automated analyses in the interpretation of myocardial perfusion studies, expert reading should continue to have a crucial role, not only in clinical decision making, but also in the assessment of prognosis.

Differences of apathy perfusion correlates between Alzheimer's disease and frontotemporal dementia. A 99mTc-HMPAO SPECT study with automated Brodmann areas analysis.

OBJECTIVES: To explore differences of apathy perfusion correlates between Alzheimer's disease (AD) and Frontotemporal dementia (FTD) using perfusion SPECT. METHODS: We studied 75 FTD and 66 AD patients. We evaluated apathy using Neuropsychiatric Inventory (NPI). We compared perfusion of BAs on left (L) and right (R) hemisphere in AD and FTD. RESULTS: Apathy in AD was significantly and negatively correlated with dorsolateral prefrontal cortex bilaterally, right anterior prefrontal cortex, inferior frontal cortex bilaterally, especially on the right, orbital part of inferior frontal gyrus bilaterally, left dorsal anterior cingulate cortex, right primary and secondary visual cortex, and with bilateral anterior and dorsolateral prefrontal cortex, inferior frontal cortex and orbital part of inferior frontal gyrus, bilaterally, bilateral anterior -ventral and dorsal- cingulate cortex, left posterior ventral cingulate cortex, right inferior, middle and anterior temporal gyri, entorhinal and parahippocampal cortex in FTD. CONCLUSIONS: Significant overlapping of apathy perfusion correlates between AD and FTD is seen in frontal areas and anterior cingulate. Right occipital cortex is also involved in AD, while right temporal cortex and left posterior cingulate are involved in FTD. Nuclear imaging could be a useful biomarker for revealing apathy underlying mechanisms, resulting in directed treatments.KEYPOINTSUnderlying neural networks and clinical manifestation of apathy may differ between AD and FTD.Apathy in AD is correlated with hypoperfusion in bilateral frontal areas, more prominent on the right, left anterior cingulate and right occipital cortex.Apathy in FTD is correlated with hypoperfusion in bilateral frontal areas, bilateral anterior cingulate, left posterior cingulate and right temporal cortex.Brain perfusion SPECT with automated BAs analysis and comparison with normal healthy subjects may provide significant information for apathy mechanisms in neurodegenerative disorders, affecting patients' treatment.

Automated Analysis vs. Expert Reading in Nuclear Cardiology: Correlations with the Angiographic Score.

Background and Objectives: Myocardial perfusion imaging (MPI) has an important role in the non-invasive investigation of coronary artery disease. The interpretation of MPI studies is mainly based on the visual evaluation of the reconstructed images, while automated quantitation methods may add useful data for each patient. However, little evidence is currently available regarding the actual incremental clinical diagnostic performance of automated MPI analysis. In the present study, we aimed to assess the correlation between automated measurements of Summed Stress Score (SSS), Summed Rest Score (SRS) and Summed Difference Score (SDS), with the corresponding expert reading values, using coronary angiography as the gold standard. Materials and Methods: The study was conducted at the Nuclear Medicine Laboratory of the University Hospital of Larissa, Larissa, Greece, οver an one-year period (January 2019-January 2020). 306 patients, with known or suspected coronary artery disease, were enrolled in the study. Each participant underwent a coronary angiography, prior to or after the scintigraphic study (within a three-month period). Either symptom-limited treadmill test, or pharmacologic testing using adenosine or regadenoson, was performed in all participants, and the scintigraphic studies were carried out using technetium 99m (99mTc) tetrofosmin (one-day stress/rest protocol). Coronary angiographies were scored according to a 4-point scoring system (angiographic score; O: normal study, 1: one-vessel disease, 2: two-vessel disease, 3: three-vessel disease). Moreover, automated measurements of SSS, SRS and SDS were derived by three widely available software packages (Emory Cardiac Toolbox, Myovation, Quantitative Perfusion SPECT). Results: Interclass Correlation Coefficients of SSS, SRS and SDS between expert reading and software packages were moderate to excellent. Visually defined SSS, SRS and SDS were significantly correlated with the corresponding results of all software packages. However, visually defined SSS, SRS and SDS were more strongly correlated with the angiographic score, indicating a better performance of expert reading when compared to automated analysis. Conclusions: Based on our results, visual evaluation continues to have a crucial role for the interpretation of MPI images. Software packages can provide automated measurements of several parameters, particularly contributing to the investigation of cases with ambiguous scintigraphic findings.

Τhe Greek Variant in APP Gene: The Phenotypic Spectrum of APP Mutations.

Mutations in the gene encoding amyloid precursor protein (APP) cause autosomal dominant inherited Alzheimer's disease (AD). We present a case of a 68-year-old female who presented with epileptic seizures, neuropsychiatric symptoms and progressive memory decline and was found to carry a novel APP variant, c.2062T>G pLeu688Val. A comprehensive literature review of all reported cases of AD due to APP mutations was performed in PubMed and Web of Science databases. We reviewed 98 studies with a total of 385 cases. The mean age of disease onset was 51.3 ± 8.3 (31-80 years). Mutations were most often located in exons 17 (80.8%) and 16 (12.2%). The most common symptoms were dementia, visuospatial symptoms, aphasia, epilepsy and psychiatric symptoms. Mutations in the ß-amyloid region, and specifically exon 17, were associated with high pathogenicity and a younger age of disease onset. We describe the second reported APP mutation in the Greek population. APP mutations may act variably on disease expression and their phenotype is heterogeneous.

Recommendations for nuclear neuroimaging of patients with neurological disorders in the COVID-19 era.

The novel coronavirus disease 2019 (COVID-19) pandemic has changed people's normal lives in a very short time causing extensive infections and mortality, which required the national health systems to be adapted to new situation. Changes in healthcare services included modifications of standard procedures in nuclear medicine departments in order to limit COVID-19 spreading and protect patients and personnel. Here, we recommend management of patients with neurological diseases and especially dementia and movement disorders, who are referred for neuroimaging with nuclear medicine techniques.

Impact of renin-angiotensin-aldosterone system polymorphisms on myocardial perfusion: Correlations with myocardial single photon emission computed tomography-derived parameters.

BACKGROUND: Renin-angiotensin-aldosterone system (RAAS) has an important role in atherosclerosis. We investigated the effects of six RAAS gene polymorphisms on myocardial perfusion. METHODS AND RESULTS: We examined 810 patients with known or suspected coronary artery disease (CAD) using stress-rest myocardial single-photon emission computed tomography. Summed stress score (SSS), summed rest score (SRS), summed difference score (SDS), transient ischemic dilation (TID), and lung/heart ratio (LHR) were recorded. The following gene polymorphisms were investigated: angiotensin-converting enzyme (ACE) insertion/deletion (I/D), angiotensinogen (AGT) M235T and T174M, angiotensin II type 1 receptor (AT1R) A1166C, renin (REN) C5312T, and angiotensin II type 2 receptor (AT2R) C3123A. The heterozygotes or homozygotes on ACE D allele were 7.54 times more likely to have abnormal SSS, while the AGT (T174M) heterozygotes were 5.19 times more likely to have abnormal SSS. The homozygotes of ACE D had significantly higher values on TID and LHR, while the AGT (T174M) heterozygotes had higher values on TID. The AT1R heterozygotes had greater odds for having SSS ≥ 3. The patients carried AT1R homozygosity of C allele had significantly higher values on TID, while heterozygotes of AT1R had significantly higher values on LHR. CONCLUSIONS: Among the polymorphisms investigated, ACE D allele had the strongest association with abnormal myocardial perfusion.

Radiolabeled mAbs as Molecular Imaging and/or Therapy Agents Targeting PSMA.

Molecular imaging and therapy is a rapidly evolving field in research and clinical medicine. The use of the exciting and attractive properties of radioisotopes for imaging and therapy has made Nuclear Medicine very significant when it comes to molecular imaging/therapy. Monoclonal Antibodies (mAbs) on the other hand are very important targeting biomolecules with high affinity that can "carry" the radioisotope of choice. Herein we make a brief overview of the radiolabeled mAbs that target prostate specific membrane antigen (PSMA) and their use in the management of patients with prostate cancer (PCa).

Myocardial perfusion and left ventricular quantitative parameters obtained using gated myocardial SPECT: Comparison of three software packages.

BACKGROUND: The aim of the present study was to compare Emory Cardiac Toolbox, Myovation, and Quantitative Gated SPECT software regarding the automatic measurements of perfusion and functional left ventricular (LV) quantitative parameters, summed stress score (SSS), perfusion defect score, LV ejection fraction (LVEF), end-diastolic volume, and end-systolic volume (ESV). METHODS AND RESULTS: 99mTc-tetrofosmin gated SPECT studies were performed in 634 consecutive patients based on the one-day stress/rest protocol. Participants were divided into subgroups according to heart size (ESV cut-off value: 25 mL), perfusion (SSS >/≤3), and other patient/protocol-related factors. LVEF was categorized as normal (≥50%), mildly moderately impaired (35-49%), and severely abnormal (<35%). The concordance between the packages was good to excellent, in overall population, ESV ≤25 mL, ESV >25 mL, and SSS >3 subgroups (intraclass correlation coefficients, ICCs 0.73-0.93). In SSS ≤3 subgroup, the correlation was excellent for LV functional parameters, but suboptimal for perfusion variables (ICCs 0.30-0.83). LVEF categorization revealed similar variability (discordance 18.1 and 11.1% for stress/rest LVEF values, respectively). Pair comparisons demonstrated considerable differences concerning all parameters for all patient subgroups. The statistical significance of our findings by ESV and SSS classifications was evaluated. CONCLUSIONS: Despite the significant concordance between software packages, considerable differences in mean values of myocardial perfusion and LV functional parameters were demonstrated.

SPECT and PET in ischemic heart failure.

Heart failure is a common clinical syndrome associated with significant morbidity and mortality worldwide. Ischemic heart disease is the leading cause of heart failure, at least in the industrialized countries. Proper diagnosis of the syndrome and management of patients with heart failure require anatomical and functional information obtained through various imaging modalities. Nuclear cardiology techniques play a main role in the evaluation of heart failure. Myocardial single photon emission computed tomography (SPECT) with thallium-201 or technetium-99 m labelled tracers offer valuable data regarding ventricular function, myocardial perfusion, viability, and intraventricular synchronism. Moreover, positron emission tomography (PET) permits accurate evaluation of myocardial perfusion, metabolism, and viability, providing high-quality images and the ability of quantitative analysis. As these imaging techniques assess different parameters of cardiac structure and function, variations of sensitivity and specificity have been reported among them. In addition, the role of SPECT and PET guided therapy remains controversial. In this comprehensive review, we address these controversies and report the advances in patient's investigation with SPECT and PET in ischemic heart failure. Furthermore, we present the innovations in technology that are expected to strengthen the role of nuclear cardiology modalities in the investigation of heart failure.

Multimodality-multiparametric brain tumors evaluation.

Brain tumors represent a vast group of lesions, originating from different neuronal cells with different degrees of aggressiveness. Despite some technological advances either pre or post-treatment, these tumors may share similar imaging findings and properties, rendering diagnosis/prognosis, an ambiguous process. Gadolinium-enhanced magnetic resonance imaging remains the gold standard for providing detailed morphologic information, but presents several limitations due to the overlap of findings, in cases such as progressive tumor and post-radiation related effects. Tumor cellularity, vascularity, proliferative activity, metabolic and functional profiles are a few of many characteristics that may further support tumor classification, but cannot be assessed by conventional imaging alone. We review the aforementioned factors and indicate how they improve tumor characterization and grading in order to design the optimal treatment strategy and better evaluate post treatment efficacy.

The prevalence of a false-positive myocardial perfusion stress SPET test in a skinny patient, induced by projection truncation.

During the last decade, technical developments in myocardial perfusion single photon emission tomography (SPET) imaging systems have significantly improved the accuracy of diagnosing coronary artery disease. Nevertheless, the patient's position and/or the acquisition protocol can affect the studies' quality, possibly leading to misdiagnoses. In HJNM and in other journals the importance of proper positioning of the heart of the patient to be examined by myocardial perfusion SPET stress/rest testing, has been emphasized. According to our knowledge, only three cases of truncation artifact during SPET myocardial perfusion imaging acquired with original SPET cameras, related to improper positioning in very thin patients, have been reported. In all cases, patients were examined according to a single day stress/rest technetium-99m-sestamibi protocol, using a dual 90 degree detector system, equipped with high resolution, parallel-hole collimators. However, several published manuscripts have underlined the significance of appropriate patients' positioning in myocardial perfusion scintigraphy using dedicated, cadmium-zinc-telluride (CZT) or small field-of-view cardiac SPET systems. A typical case is that of a 47 years old man (height 187cm, weight 67kg), heavy smoker, with atypical chest pain. He exercised very well according to the Bruce protocol, achieving 95% of maximal age-predicted heart-rate and a technetium-99m-tetrofosmin ((99m)Tc-TF) myocardial perfusion imaging with 370MBq of (99m)Tc-TF followed with a dual head camera (Infinia GE, USA), equipped with low-energy, high-resolution, parallel-hole collimators at 90° (L-mode configuration). Projection images were obtained from 45° RAO to 45° LPO position, in step and shoot mode (60 projections, 30sec per projection; matrix 64×64 and zoom 1.3). Auto body contour was not used. Unprocessed raw data, showed neither patient motion nor significant extracardiac activity that could result in false positive defects on myocardial perfusion stress images. However, truncation at the apex of the heart was observed. In detail, truncation of activity of apical portion of the heart from frame 45-60 (detector 1) and frames 1-5 (detector 2) was noticed. Processed stress images demonstrated a severe defect in the apex and the apical part of the anteroseptal wall. Moreover, less intense defects were observed in the inferior and septal walls. All acquisition parameters were double checked and a possible error regarding the "zoom" was ruled out. Hence, it became evident that the aforementioned artifact has originated from an eccentric patient's position and thus some heart projections were missed. A second stress acquisition was performed after repositioning the patient with emphasis on positioning the heart at the center of the field of view. As a result, improvement of the above mentioned defects, mainly in the apex and the apical anteroseptal wall. In the literature, a number of recent studies have mentioned the effect of the truncation artifact even with newly equipped gamma cameras, emphasizing the importance of the heart being in the field of view throughout the acquisition procedure. Few of them used parallel-hole collimation. In conclusion, it is suggested that in cases of very thin patients it is often necessary to avoid truncation artefacts by correctly positioning the patient's heart.

Multifocal septic osteomyelitis mimicking skeletal metastatic disease in a patient with prostate cancer.

We present an unusual case of a 59 years old patient with prostate cancer, who was referred to our hospital with pleurodenia, low back and other sites of bone ostalgia, for bone scintiscan. The patient underwent a whole body bone scanning after the intravenous administration of 740MBq (99m)Tc-methylene diphosphonate (MDP). The main findings of the study were: increased radiotracer uptake at the T5, T9-T10 vertebrae, the head of the 11th rib and the area of the left sternoclavicular joint (SCJ), which were initially attributed to skeletal metastatic lesions. Another "hot" area in the left knee, was consistent with severe arthritis. Physical examination revealed fever up to 38.7°C, tenderness and swelling of his left knee and various painful sites. Due to persistent fever and markedly raised inflammatory markers (ESR 102mm/h, CRP 73.8mg/L, WBC 16.800 cells/µ L - neutrophils 78%, lymphocytes 15%, monocytes 5%, eosinophils 1%), the patient was further referred for a magnetic resonance (MR) scan with specific interest on the thoracic spine and the SCJ. In the sagittal short-tau inversion recovery (STIR) MR image, abnormally high signal involving both T9 and T10 vertebral bodies due to bone marrow oedema and irregularity of the endplates with focal destruction areas, were observed. The T9-T10 intervertebral disc had an abnormally high signal suggestive of "hot disc" sign and also a prevertebral soft tissue mass abutting the anterior aspect of the involved vertebral bodies. The axial T1-weighted image with fat saturation post gadolinium (Gd), revealed diffuse strong enhancement in the vertebral body, the paraspinal soft tissue mass and the adjacent right rib. Circumferential epidural enhancement indicative of intra-canal spread of the infection, was also noticed. Additional MR sequences covered the level of the SCJ. Extensive subarticular and soft tissue changes with fluid collection and bone oedema of the left SCJ were shown with the typical pattern of diffuse enhancement suggestive of septic arthritis. The MR imaging findings combined with the scintigraphic findings were consistent with subacute multifocal septic arthritis involving the axial skeleton, as a pyogenic spondylodiscitis at the T9-T10 level, the left SCJ joint and the left knee joint. Subsequently, aspiration of the SCJ and the left knee joint was performed. A purulent fluid was drained and sent to microbiology. The sample revealed 96.000 cells/µL (95% neutrophils) and methicillin-resistant Staphylococcus aureus (MRSA). The patient received intravenous vancomucin (2gr. twice a day for 14 days) and subsequently the dose was adjusted to maintain the vancomucin serum levels between 17 and 20mcg/mL. The total treatment duration was 12 weeks. Four months later the patient had fully recovered and his blood tests were normal. The patient had not been referred to an oncology department yet, as the onset of the arthritis occurred about two weeks after the diagnosis of prostate cancer. In conclusion, we present a patient with known malignancy, fever, skeletal pain and multiple bone lesions in the (99m)Tc-MDP and the MRI examination, not due to metastatic disease but to septic arthritis.

Metabolism-related cytokine and hormone levels in the serum of patients with myelodysplastic syndromes.

BACKGROUND: A number of cytokines secreted from the bone marrow stromal cells and circulating hormones related to bone, adipose tissue and glucose metabolism might be involved in the pathogenesis of myelodysplastic syndromes (MDS). METHODS: Serum levels of cytokines related to the metabolism of bone tissue [osteocalcin and parathyroid hormone (PTH)], adipose tissue (adiponectin, leptin and ghrelin) and glucose [insulin and insulin-like growth factor-1 (IGF-1)] were determined in 72 patients suffering from MDS, mostly of the low-risk group according to FAB classification, and 41 healthy individuals (controls). RESULTS: Adiponectin and osteocalcin serum levels were significantly elevated in the MDS patients. Leptin, insulin and IGF-1 serum levels were reduced. No difference was found in the serum levels of PTH and ghrelin. Leptin levels were reversibly associated with patient blast count. CONCLUSION: Increased serum levels of adiponectin and low levels of IGF-1 in MDS patients may counterbalance the increased rate of apoptosis in the pool of hematopoietic progenitors. Osteocalcin secreted by osteoblasts regulates the renewal and proliferation of hematopoietic stem cells. Hormones and cytokines either secreted by the cells of the bone marrow stroma or transferred by the microcirculation act on hematopoietic progenitors and may regulate their differentiation, apoptosis and proliferation rate in MDS.

SPECT and PET imaging of meningiomas.

Meningiomas arise from the meningothelial cells of the arachnoid membranes. They are the most common primary intracranial neoplasms and represent about 20% of all intracranial tumors. They are usually diagnosed after the third decade of life and they are more frequent in women than in men. According to the World Health Organization (WHO) criteria, meningiomas can be classified into grade I meningiomas, which are benign, grade II (atypical) and grade III (anaplastic) meningiomas, which have a much more aggressive clinical behaviour. Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are routinely used in the diagnostic workup of patients with meningiomas. Molecular Nuclear Medicine Imaging with Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) could provide complementary information to CT and MRI. Various SPECT and PET tracers may provide information about cellular processes and biological characteristics of meningiomas. Therefore, SPECT and PET imaging could be used for the preoperative noninvasive diagnosis and differential diagnosis of meningiomas, prediction of tumor grade and tumor recurrence, response to treatment, target volume delineation for radiation therapy planning, and distinction between residual or recurrent tumour from scar tissue.

Anosognosia in Dementia: Evaluation of Perfusion Correlates Using 99mTc-HMPAO SPECT and Automated Brodmann Areas Analysis.

(1) Background: Considerable inconsistency exists regarding the neural substrates of anosognosia in dementia in previous neuroimaging studies. The purpose of this study was the evaluation of anosognosia perfusion correlates across various types of dementia using automated Brodmann areas (BAs) analysis and comparison with a database of normal subjects. (2) Methods: We studied 72 patients: 32 with Alzheimer's disease, 26 with frontotemporal dementia-FTD (12 behavioral FTD, 9 semantic FTD, 5 Progressive Non-Fluent Aphasia), 11 with corticobasal syndrome, and 3 with progressive supranuclear palsy. Addenbrook's Cognitive Examination-Revised (ACE-R) mean(±SD) was 55.6(±22.8). For anosognosia measurement, the Anosognosia Questionnaire-Dementia was used. Total anosognosia score mean(±SD) was 22.1(±17.9), cognitive anosognosia score mean(±SD) was 18.1(±15.1) and behavioral-mood anosognosia score mean(±SD) was 3.3(±4.7). (3) Results: Higher anosognosia total score was associated with hypoperfusion in the inferior temporal, anterior cingulate, and inferior frontal cortices of the right hemisphere (BAs 20R, 24R, 32R, 45R). Higher anosognosia cognitive score was correlated with hypoperfusion in the left middle and anterior temporal cortices, and right dorsal anterior cingulate cortex (BAs 21L, 22L, 32R). No association was found with behavioral-mood anosognosia. (4) Conclusions: Automated analysis of brain perfusion Single Photon Emission Computed Tomography could be useful for the investigation of anosognosia neural correlates in dementia.

Fahr's syndrome due to hypoparathyroidism revisited: A case of parkinsonism and a review of all published cases.

INTRODUCTION: Fahr's syndrome due to hypoparathyroidism refers to bilateral basal ganglia (BG) calcifications and manifests with movement disorders, seizures, cognitive and behavioral symptoms. CASE PRESENTATION: We report a case of a 74-year-old woman, who presented with parkinsonism due to post-surgical hypoparathyroidism and normal DaT scan, despite extensive calcifications of the BG, periventricular white matter, and cerebellum. METHODS: A comprehensive literature review of all reported cases of Fahr's syndrome due to hypoparathyroidism was conducted in the electronic databases PubMed and Web of science. Moreover, demographic and clinical characteristics of the patients overall were calculated and associated with radiological findings. RESULTS: We reviewed a total of 223 cases with Fahr's syndrome due to hypoparathyroidism (124 female, 99 male). Mean age on presentation was 44.6 ± 17.7 years. Thirty nine percent of patients had idiopathic hypoparathyroidism, 35.4 % acquired and 25.6 % pseudohypoparathyroidism. Almost half of the patients had tetany, seizures or a movement disorder and approximately 40 % neuropsychiatric symptoms. The patients with a movement disorder had a 2.23 likelihood of having neuropsychiatric symptoms as well (OR 2.23, 95 % CI 1.29-3.87). Moreover, there was a statistically significant association between the phenotype severity (i.e. the presence of more than one symptom) and the extent of brain calcifications (χ2 = 32.383, p = 0.009). CONCLUSION: Fahr's syndrome is a rare disorder, which nonetheless manifests with several neurological symptoms. A head CT should be considered for patients with hypoparathyroidism and neurological symptoms. More studies using DaT scan are needed to elucidate the effects of calcifications on the dopaminergic function of the BG.