Is oropharyngoesophageal scintigraphy the method of choice for assessing dysphagia in systemic sclerosis? A single center experience.

OBJECTIVES: To evaluate the performance of oropharyngoesophageal scintigraphy (OPES) in the assessment of dysphagia in patients with systemic sclerosis (SSc), and to compare OPES results with those of barium esophagogram. METHODS: Adult SSc patients who underwent OPES for the assessment of dysphagia were enrolled. OPES was performed with both liquid and semisolid boluses and provided information regarding oropharyngeal transit time, esophageal transit time (ETT), oropharyngeal retention index (OPRI), esophageal retention index (ERI), and site of bolus retention. Barium esophagogram results were also collected. RESULTS: Fifty-seven SSc patients (87.7% female, mean age 57.7 years) with dysphagia were enrolled. OPES identified at least one alteration in each patient and findings were generally worse for the semisolid bolus. Esophageal motility was widely impaired with 89.5% of patients with an increased semisolid ERI, and middle-lower esophagus was the most frequent site of bolus retention. However, oropharyngeal impairment was highlighted by widespread increased OPRI, especially in anti-topoisomerase I positivity. Older patients and with longer disease duration presented slower semisolid ETT (p = 0.029 and p = 0.002, respectively). Eleven patients with dysphagia had a negative barium esophagogram: all of them presented some alterations in OPES parameters. CONCLUSION: OPES revealed a marked SSc esophageal impairment, in terms of both slowed transit time and increased bolus retention, but also shed light on oropharyngeal swallowing alterations. OPES showed high sensitivity, being able to detect swallowing alterations in dysphagic patients with negative barium esophagogram. Therefore, the use of OPES for the assessment of SSc-related dysphagia in clinical practice should be promoted.

Brain effect of bariatric surgery in people with obesity.

BACKGROUND/OBJECTIVES: The link between obesity and brain function is a fascinating but still an enigmatic topic. We evaluated the effect of Roux-en-Y gastric bypass (RYGB) on peripheral glucose metabolism, insulin sensitivity, brain glucose utilization and cognitive abilities in people with obesity. SUBJECTS/METHODS: Thirteen subjects with obesity (F/M 11/2; age 44.4 ± 9.8 years; BMI 46.1 ± 4.9 kg/m2) underwent 75-g OGTT during a [18F]FDG dynamic brain PET/CT study at baseline and 6 months after RYGB. At the same timepoints, cognitive performance was tested with Mini Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Trail making test (TMT) and Token test (TT). Glucose, insulin, C-peptide, GLP-1, GIP, and VIP levels were measured during OGTT. Leptin and BDNF levels were measured before glucose ingestion. RESULTS: RYGB resulted in significant weight loss (from 46.1 ± 4.9 to 35.3 ± 5.0 kg/m2; p < 0.01 vs baseline). Insulin sensitivity improved (disposition index: from 1.1 ± 0.2 to 2.9 ± 1.1; p = 0.02) and cerebral glucose metabolic rate (CMRg) declined in various brain areas (all p ≤ 0.01). MMSE and MoCA score significantly improved (p = 0.001 and p = 0.002, respectively). TMT and TT scores showed a slight improvement. A positive correlation was found between CMRg change and HOMA-IR change in the caudate nucleus (ρ = 0.65, p = 0.01). Fasting leptin decreased (from 80.4 ± 13.0 to 16.1 ± 2.4 ng/dl; p = 0.001) and correlated with CMRg change in the hippocampus (ρ = 0.50; p = 0.008). CMRg change was correlated with cognitive scores changes on the TMT and TT (all p = 0.04 or less). CONCLUSIONS: Bariatric surgery improves CMRg directly related to a better cognitive testing result. This study highlights the potential pleiotropic effects of bariatric surgery. TRIAL REGISTRY NUMBER: NCT03414333.

Validation of FDG-PET datasets of normal controls for the extraction of SPM-based brain metabolism maps.

PURPOSE: An appropriate healthy control dataset is mandatory to achieve good performance in voxel-wise analyses. We aimed at evaluating [18F]FDG PET brain datasets of healthy controls (HC), based on publicly available data, for the extraction of voxel-based brain metabolism maps at the single-subject level. METHODS: Selection of HC images was based on visual rating, after Cook's distance and jack-knife analyses, to exclude artefacts and/or outliers. The performance of these HC datasets (ADNI-HC and AIMN-HC) to extract hypometabolism patterns in single patients was tested in comparison with the standard reference HC dataset (HSR-HC) by means of Dice score analysis. We evaluated the performance and comparability of the different HC datasets in the assessment of single-subject SPM-based hypometabolism in three independent cohorts of patients, namely, ADD, bvFTD and DLB. RESULTS: Two-step Cook's distance analysis and the subsequent jack-knife analysis resulted in the selection of n = 125 subjects from the AIMN-HC dataset and n = 75 subjects from the ADNI-HC dataset. The average concordance between SPM hypometabolism t-maps in the three patient cohorts, as obtained with the new datasets and compared to the HSR-HC standard reference dataset, was 0.87 for the AIMN-HC dataset and 0.83 for the ADNI-HC dataset. Pattern expression analysis revealed high overall accuracy (> 80%) of the SPM t-map classification according to different statistical thresholds and sample sizes. CONCLUSIONS: The applied procedures ensure validity of these HC datasets for the single-subject estimation of brain metabolism using voxel-wise comparisons. These well-selected HC datasets are ready-to-use in research and clinical settings.

Vesicular monoamine transporters expression in pheochromocytomas and paragangliomas according to scintigraphy and positron emission tomography behavior.

BACKGROUND: The expression of vesicular catecholamine transporters (VMAT1 and 2) in pheochromocytomas (PHEOs) and paragangliomas (PGLs) and the possible relationships with [18F]FDOPA PET/CT and [123I]MIBG scintigraphy uptake are unknown. Our purpose was to investigate possible correlations of either VMAT1 and VMAT2 expression with the functional imaging in patients with PHEOs and PGLs. METHODS: An observational 3-year time study was performed by enrolling 31 consecutive patients with PHEO (N.=17) or PGL (N.=14). They underwent the same diagnostic work-up; moreover, [123I]MIBG SPECT/CT (N.=20) and [18F]FDOPA PET/CT (N.=14) were performed in a subset of patients. After surgery, routine histology and semiquantitative analysis of VMAT1/VMAT2 immunoreactivity were carried out in all cases. RESULTS: VMAT1 immunoreactivity was found in all tumors, but two PHEOs. VMAT1 immunoreactivity was higher in PGLs than in PHEOs, though at not significant extent. Elevated VMAT2 immunoreactivity score was present in all but two negative tumors. Normal [123I]-MIBG uptake was independent from VMAT1/2 immunoreactivity. Patients undergoing [18F]FDOPA PET/CT showed a high score level of both VMATs and were detected by the technique in all cases. CONCLUSIONS: VMAT1 and VMAT2 are highly expressed in most tumors, though VMAT1 immunoreactivity is apparently prevalent in PGLs as compared to PHEOs. Presence and expression of VMAT1 and VMAT2 are not limiting factors for MIBG uptake. The status of VMAT expression might help to understand why the more frequently used radiotracers do not always have the expected diagnostic performance. Finally, the present study points out the importance of developing new radiotracers with higher sensitivity, specificity and accuracy consequently reducing healthcare costs.

Is DAT imaging abnormality in normal pressure hydrocephalus always suggestive of degeneration?

Idiopathic normal pressure hydrocephalus (iNPH) is a debated entity with controversial pathogenesis, diagnostic criteria, and predictors of response after ventriculoperitoneal shunt (VPS). Parkinsonian signs are frequently reported in the clinical picture, sometimes due to the coexistence of an underlying neurodegenerative parkinsonism and sometimes in the absence thereof. To distinguish these two scenarios is crucial, since they may carry different long-term response to CSF drainage. 123I-FP-CIT-SPECT was believed to be helpful in this regard, however its role in predicting surgical outcome has been disputed. We illustrate a patient presented with gait disturbance, urinary incontinence, and asymmetrical parkinsonian signs, who underwent a 3T brain MRI and a 123I-FP-CIT-SPECT. VPS was performed. The patient repeated a 123I-FP-CIT-SPECT, 18 months after the operation, and was clinically followed up for 24 months. Our patient displayed clinical and radiological criteria for iNPH and an abnormal asymmetrical uptake in 123I-FP-CIT-SPECT, consistent with her asymmetrical parkinsonism. However, the organization of the substantia nigra studied with iron-sensitive sequences in 3T brain MRI scan appeared intact. The patient revealed an improvement both clinically and in 123I-FP-CIT-SPECT at postsurgical follow-up. Our report suggests that abnormal 123I-FP-CIT-SPECT may not necessarily reveal an overlap with neurodegenerative parkinsonism; its partial reversibility may suggest that the mechanical effect exerted on the striatum by ventriculomegaly ultimately leads to downregulation of dopaminergic transporters which may improve after VPS.

Coffee Consumption and Cancer Risk: An Assessment of the Health Implications Based on Recent Knowledge.

A significant number of studies suggest that coffee consumption reduces cancer risk. This beneficial effect is usually ascribed to the presence of polyphenolic antioxidants and anti-inflammatory agents, including caffeine, cafestol, kahweol, and chlorogenic acids. To summarize recent literature on this subject, we performed a bibliographic search in PubMed and Embase over the period January 2005 to December 2020 to identify cohort studies and meta-analysis (with data collection ensuring quality of selected reports) that could provide quantitative data on the relationship between coffee consumption and common cancers. The totality of eligible scientific articles supports the evidence that coffee intake is inversely associated with risk of hepatocellular cancer and, to a slight extent, risk of breast cancer among postmenopausal women. As to the association with other organs, including the esophagus, pancreas, colorectum, kidneys, bladder, ovaries, and prostate, the results are less clear as reports reveal conflicting results or statistically nonsignificant data. Therefore, this overview does not provide broad-based conclusions. Important uncertainties include general study design, inhomogeneous patient sampling, different statistical analysis (deliberate), misreporting of socioeconomic status, education, coffee-brewing methods, consumption of caffeinated or decaffeinated coffee, smoking habits, and alcohol intake. Clearly, more epidemiologic research needs to be conducted before solid science-based recommendations can be made with regard to coffee consumption.

Dopamine Transporter, Age, and Motor Complications in Parkinson's Disease: A Clinical and Single-Photon Emission Computed Tomography Study.

BACKGROUND: Previous molecular imaging studies comparing dopamine function in vivo between early-onset PD and late-onset PD patients have shown contradictory results, presumably attributable to the aging-related decline in nigrostriatal function. OBJECTIVES: (1) To investigate baseline dopamine transporter availability in early-onset PD (<55 years) and late-onset PD (>70 years) patients, z-scores values of putamen and caudate [123 I]-ioflupane uptake were calculated using the respective age-matched controls in order to correct for early presynaptic compensatory mechanisms and age-related dopamine neuron loss; (2) to examine the associations of such baseline single-photon emission computed tomography measures with the emergence of late-disease motor complications. METHODS: In this retrospective study, 105 de novo PD patients who underwent [123 I]-ioflupane single-photon emission computed tomography at time of diagnosis were divided into three tertile groups according to age at disease onset (35 early-onset PD and 40 late-onset PD patients). Z-scores were compared between the two groups, and their predictive power for motor complications (during a mean follow-up of 7 years) was evaluated using Cox proportional hazard models. RESULTS: Despite a less-severe motor phenotype, early-onset PD patients exhibited more reduced [123 I]-ioflupane binding in the putamen and had a higher and earlier risk for developing motor complications than those with late-onset PD. Lower [123 I]-Ioflupane uptake in the putamen and caudate increased the risk of motor complications. CONCLUSIONS: Our findings indicate that a lower dopamine transporter binding in early-onset PD predicts the later development of motor complications, but it is not related to severity of motor symptoms, suggesting age-related differences in striatal compensatory mechanisms in PD. © 2020 International Parkinson and Movement Disorder Society.

Association between semiquantitative PET parameters and molecular subtypes of breast invasive ductal carcinoma.

BACKGROUND: Molecular subtypes of breast cancer have been proposed since 2012. The correlation between various baseline [18F]fluorodeoxyglucose ([18F]FDG) uptake parameters, including total lesion glycolysis (TLG), and molecular subtypes of primary breast cancer lesions in patients with invasive ductal cancer will be investigated. METHODS: Staging [18F]FDG PET/CT for breast invasive ductal carcinoma were retrospectively evaluated. Breast lesions were examined for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation index (Ki-67). Breast tumors were classified into five molecular subtypes: Luminal A, Luminal B-HER2(-), Luminal B-HER2(+), HER2(+) and Basal or Triple Negative cancers. The correlations between tumor characteristics and PET semiquantitative data of primary breast lesion (SUVmean, SUVmax, Mean tumor volume (MTV), TLG) were assessed. Specific Breast Uptake Ratio (SBUR) is used as a new quantification method of breast uptake to correct for physiological background activity. RESULTS: Fifty-eight patients were included. TLG was significantly higher in triple negative group when compared with luminal A (P<0.01). Significantly higher uptake was found in triple negative lesions when compared with luminal B-HER2(-) and luminal B-HER2(+) categories using SUVmax, SUVmean and TLG (all P<0.05). Conversely, no statistically significant difference for [18F]FDG uptake was observed between all other molecular subtypes. No value of SBUR in terms of correlation with histopathological parameters was demonstrated. CONCLUSIONS: TLG was superior to SUVmax and SUVmean in differentiating between triple negative breast cancer lesions and all other molecular subtypes. SBUR was not different statistically between various molecular subtypes.

The Precuneus - A Witness for Excessive Aß Gathering in Alzheimer's Disease Pathology.

Evidence of cortical beta-amyloid (Aß) load, assessed by Aß positron emission tomography (Aß-PET), is an established in vivo biomarker of Alzheimer's disease (AD)-related pathophysiology. Qualitative assessment of Aß-PET provides binary information; meanwhile semiquantitative approaches require a parcellation of PET image either manually or by placement of atlas-based volumes of interest. We supposed that a whole-brain approach with voxel-by-voxel standardized uptake value ratio (SUVr) parametric images may better elucidate the spatial trajectories of Aß burden along the continuum of AD. METHODS: We recruited 32 subjects with a diagnosis of probable AD dementia (ADD, n = 20) and mild cognitive impairment due to AD (MCI-AD, n = 12) according to the NIA-AA 2011 criteria. We also enrolled a control group of 6 cognitively healthy individuals (HCs) with preserved cognitive functions and negative Aß-PET scan. The PET images were spatially normalized using the AV45 PET template in the MNI brain space. Subsequently, parametric SUVr images were calculated using the whole cerebellum as a reference region. A voxel-wise analysis of covariance was used to compare (between groups) the Αß distribution pattern considering age as a nuisance covariate. RESULTS: Both ADD and MCI-AD subjects showed a widespread increase in radiotracer uptake when compared with HC participants (p < 0.001, uncorrected). After applying a multiple comparison correction (p < 0.05, corrected), a relative large cluster of increased [18F]-flor-betapir uptake was observed in the precuneus in the ADD and MCI-AD groups compared to HCs. Voxel-wise regression analysis showed a significant positive linear association between the voxel-wise SUVr values and the disease duration. CONCLUSIONS: The voxel-wise semiquantitative analysis shows that the precuneus is a region with higher vulnerability to Aß depositions when compared to other cortical regions in both MCI-AD and ADD subjects. We think that the precuneus is a promising PET-based outcome measure for clinical trials of drugs targeting brain Aß. We found a positive association between the overall Aß-PET SUVr and the disease duration suggesting that the region-specific slow saturation of Aß deposition continuously takes place as the disease progresses.

Neuroimaging in Parkinson's disease: focus on substantia nigra and nigro-striatal projection.

PURPOSE OF REVIEW: The diagnosis of Parkinson disease is based on clinical features; however, unmet need is an imaging signature for Parkinson disease and the early differential diagnosis with atypical parkinsonisms. A summary of the molecular imaging and MRI recent evidences for Parkinson disease diagnosis will be presented in this review. RECENT FINDINGS: The nigro-striatal dysfunction explored by dopamine transporter imaging is not a mandatory diagnostic criterion for Parkinson disease, recent evidence supported its utility as in-vivo proof of degenerative parkinsonisms, and there might be compensatory mechanisms leading to an early overestimation. The visualization of abnormalities in substantia nigra by MRI has been recently described as sensitive and specific tool for Parkinson disease diagnosis, even in preclinical conditions, whereas it is not useful for distinguishing between Parkinson disease and atypical parkinsonisms. The relationship between the nigral anatomical changes, evaluated as structural alterations or neuromelanin signal decrease and the dopaminergic nigro-striatal function needs to be further clarified. SUMMARY: With the hopeful advent of potential neuroprotective drugs for PD, it is crucial to have imaging measures that are able to detect at risk subjects. Moreover it is desirable to increase the knowledge about which measure better predicts the probability and the time of clinical conversion to PD.

(123) I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane single photon emission computed tomography and (123) I-metaiodobenzylguanidine myocardial scintigraphy in differentiating dementia with lewy bodies from other dementias: A comparative study.

OBJECTIVE: To compare the diagnostic value of striatal (123) I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ((123) I-FP-CIT) single photon emission computed tomography (SPECT) and (123) I-metaiodobenzylguanidine ((123) I-MIBG) myocardial scintigraphy in differentiating dementia with Lewy bodies (DLB) from other dementia types. METHODS: This prospective longitudinal study included 30 patients with a clinical diagnosis of DLB and 29 patients with non-DLB dementia (Alzheimer disease, n = 16; behavioral variant frontotemporal dementia, n = 13). All patients underwent (123) I-FP-CIT SPECT and (123) I-MIBG myocardial scintigraphy within a few weeks of clinical diagnosis. All diagnoses at each center were agreed upon by the local clinician and an independent expert, both unaware of imaging data, and re-evaluated after 12 months. Each image was visually classified as either normal or abnormal by 3 independent nuclear physicians blinded to patients' clinical data. RESULTS: Overall, sensitivity and specificity to DLB were respectively 93% and 100% for (123) I-MIBG myocardial scintigraphy, and 90% and 76% for (123) I-FP-CIT SPECT. Lower specificity of striatal compared to myocardial imaging was due to decreased (123) I-FP-CIT uptake in 7 non-DLB subjects (3 with concomitant parkinsonism) who had normal (123) I-MIBG myocardial uptake. Notably, in our non-DLB group, myocardial imaging gave no false-positive readings even in those subjects (n = 7) with concurrent medical illnesses (diabetes and/or heart disease) supposed to potentially interfere with (123) I-MIBG uptake. INTERPRETATION: (123) I-FP-CIT SPECT and (123) I-MIBG myocardial scintigraphy have similar sensitivity for detecting DLB, but the latter appears to be more specific for excluding non-DLB dementias, especially when parkinsonism is the only "core feature" exhibited by the patient. Our data also indicate that the potential confounding effects of diabetes and heart disease on (123) I-MIBG myocardial scintigraphy results might have been overestimated. Ann Neurol 2016;80:368-378.

(18)F-FDG PET/CT quantification in head and neck squamous cell cancer: principles, technical issues and clinical applications.

(18)F-FDG PET/CT plays a crucial role in the diagnosis and management of patients with head and neck squamous cell cancer (HNSCC). The major clinical applications of this method include diagnosing an unknown primary tumour, identifying regional lymph node involvement and distant metastases, and providing prognostic information. (18)F-FDG PET/CT is also used for precise delineation of the tumour volume for radiation therapy planning and dose painting, and for treatment response monitoring, by detecting residual or recurrent disease. Most of these applications would benefit from a quantitative approach to the disease, but the quantitative capability of (18)F-FDG PET/CT is still underused in HNSCC. Innovations in PET/CT technology promise to overcome the issues that until now have hindered the employment of dynamic procedures in clinical practice and have limited "quantification" to the evaluation of standardized uptake values (SUV), de facto a semiquantitative parameter, the limits of which are well known to the nuclear medicine community. In this paper the principles of quantitative imaging and the related technical issues are reviewed so that professionals involved in HNSCC management can reflect on the advantages of "true" quantification. A discussion is then presented on how semiquantitative information is currently used in clinical (18)F-FDG PET/CT applications in HNSCC, by discussing the improvements that could be obtained with more advanced and "personalized" quantification techniques.

Mozart, music and medicine.

According to the first publication in 1993 by Rauscher et al. [Nature 1993;365:611], the Mozart effect implies the enhancement of reasoning skills solving spatial problems in normal subjects after listening to Mozart's piano sonata K 448. A further evaluation of this effect has raised the question whether there is a link between music-generated emotions and a higher level of cognitive abilities by mere listening. Positron emission tomography and functional magnetic resonance imaging have revealed that listening to pleasurable music activates cortical and subcortical cerebral areas where emotions are processed. These neurobiological effects of music suggest that auditory stimulation evokes emotions linked to heightened arousal and result in temporarily enhanced performance in many cognitive domains. Music therapy applies this arousal in a clinical setting as it may offer benefits to patients by diverting their attention from unpleasant experiences and future interventions. It has been applied in the context of various important clinical conditions such as cardiovascular disorders, cancer pain, epilepsy, depression and dementia. Furthermore, music may modulate the immune response, among other things, evidenced by increasing the activity of natural killer cells, lymphocytes and interferon-γ, which is an interesting feature as many diseases are related to a misbalanced immune system. Many of these clinical studies, however, suffer from methodological inadequacies. Nevertheless, at present, there is moderate but not altogether convincing evidence that listening to known and liked music helps to decrease the burden of a disease and enhances the immune system by modifying stress.

Intraoperative Radioguided Localization of an Occult Neuroendocrine Tumor of the Ileum.

ABSTRACT: We report the intraoperative radioguided localization of an occult well-differentiated neuroendocrine tumor of the ileum in a patient with a known neuroendocrine lymphonodal metastasis in the mesentery. Preoperative imaging included CT, PET/CT with 68 Ga-DOTATOC, and SPECT/CT with 99m Tc-HYNICTOC. These scans revealed morphological and functional properties of the primary tumor localized in the ileum. The day after IV 99m Tc-HYNICTOC injection, the patient underwent surgery, and the target lesion was intraoperatively detected by a collimated handheld γ-probe. Postoperative pathology examination confirmed the target lesion to be a neuroendocrine tumor of the ileum.

Can FDG-PET assess the response to chemotherapy and predict tissue necrosis in osteosarcoma and Ewing sarcoma?

INTRODUCTION: Osteosarcoma (OS) and Ewing sarcoma (ES) represent the pediatric population's most common malignant bone tumors. 18-Fluorodeoxyglucose positron emission tomography has been shown to be effective in both the diagnostic and staging phases of cancer treatment. In recent years, some studies have also explored the possibility that FDG-PET could have a prognostic role.

Advancing Pediatric Sarcomas through Radiomics: A Systematic Review and Prospective Assessment Using Radiomics Quality Score (RQS) and Methodological Radiomics Score (METRICS).

Pediatric sarcomas, rare malignancies of mesenchymal origin, pose diagnostic and therapeutic challenges. In this review, we explore the role of radiomics in reshaping our understanding of pediatric sarcomas, emphasizing methodological considerations and applications such as diagnostics and predictive modeling. A systematic review conducted up to November 2023 identified 72 papers on radiomics analysis in pediatric sarcoma from PubMed/MEDLINE, Web of Knowledge, and Scopus. Following inclusion and exclusion criteria, 10 reports were included in this review. The studies, predominantly retrospective, focus on Ewing sarcoma and osteosarcoma, utilizing diverse imaging modalities, including CT, MRI, PET/CT, and PET/MRI. Manual segmentation is common, with a median of 35 features extracted. Radiomics Quality Score (RQS) and Methodological Radiomics Score (METRICS) assessments reveal a consistent emphasis on non-radiomic features, validation criteria, and improved methodological rigor in recent publications. Diagnostic applications dominate, with innovative studies exploring prognostic and treatment response aspects. Challenges include feature heterogeneity and sample size variations. The evolving landscape underscores the need for standardized methodologies. Despite challenges, the diagnostic and predictive potential of radiomics in pediatric oncology is evident, paving the way for precision medicine advancements.

Sentinel Lymph Node Mapping in Lung Cancer: A Pilot Study for the Detection of Micrometastases in Stage I Non-Small Cell Lung Cancer.

Lymphadenectomy represents a fundamental step in the staging and treatment of non-small cell lung cancer (NSCLC). To date, the extension of lymphadenectomy in early-stage NSCLC is a debated topic due to its possible complications. The detection of sentinel lymph nodes (SLNs) is a strategy that can improve the selection of patients in which a more extended lymphadenectomy is necessary. This pilot study aimed to refine lymph nodal staging in early-stage NSCLC patients who underwent robotic lung resection through the application of innovative intraoperative sentinel lymph node (SLN) identification and the pathological evaluation using one-step nucleic acid amplification (OSNA). Clinical N0 NSCLC patients planning to undergo robotic lung resection were selected. The day before surgery, all patients underwent radionuclide computed tomography (CT)-guided marking of the primary lung lesion and subsequently Single Photon Emission Computed Tomography (SPECT) to identify tracer migration and, consequently, the area with higher radioactivity. On the day of surgery, the lymph nodal radioactivity was detected intraoperatively using a gamma camera. SLN was defined as the lymph node with the highest numerical value of radioactivity. The OSNA amplification, detecting the mRNA of CK19, was used for the detection of nodal metastases in the lymph nodes, including SLN. From March to July 2021, a total of 8 patients (3 female; 5 male), with a mean age of 66 years (range 48-77), were enrolled in the study. No complications relating to the CT-guided marking or preoperative SPECT were found. An average of 5.3 lymph nodal stations were examined (range 2-8). N2 positivity was found in 3 out of 8 patients (37.5%). Consequently, pathological examination of lymph nodes with OSNA resulted in three upstages from the clinical IB stage to pathological IIIA stage. Moreover, in 1 patient (18%) with nodal upstaging, a positive node was intraoperatively identified as SLN. Comparing this protocol to the usual practice, no difference was found in terms of the operating time, conversion rate, and complication rate. Our preliminary experience suggests that sentinel lymph node detection, in association with the accurate pathological staging of cN0 patients achieved using OSNA, is safe and effective in the identification of metastasis, which is usually undetected by standard diagnostic methods.

Weighted registration of 123I-FP-CIT SPECT images improves accuracy of binding potential estimates in pathologically low striatal uptake.

To test whether the use of a striatum weighted image may improve registration accuracy and diagnostic outcome in patients with parkinsonian syndromes (PS), weighted images were generated by increasing signal intensity of striatal voxels and used as intermediate dataset for co-registering the brain image onto template. Experimental validation was performed using an anthropomorphic striatal phantom. (123)I-FP-CIT SPECT binding ratios were manually determined in 67 PS subjects and compared to those obtained using unsupervised standard (UWR) and weighted registered (WR) approach. Normalized cost function was used to evaluate the accuracy of phantom and subjects registered images to the template. Reproducibility between unsupervised and manual ratios was assessed by using intra-class correlation coefficient (ICC) and Bland and Altman analysis. Correlation coefficient was used to assess the dependence of semi-quantitative ratios on clinical findings. Weighted method improves accuracy of brain registration onto template as determined by cost function in phantom (0.86 ± 0.06 vs. 0.98 ± 0.02; Student's t-test, P = 0.04) and in subject scans (0.69 ± 0.06 vs. 0.53 ± 0.06; Student's t-test, P < 0.0001). Agreement between manual and unsupervised derived binding ratios as measured by ICC was significantly higher on WR as compared to UWR images (0.91 vs. 0.76). Motor UPDRS score was significantly correlated with manual and unsupervised derived binding potential. In phantom, as well as in subjects studies, correlations were more significant using the WR method (BPm: R(2) = 0.36, P = 0.0001; BPwr: R(2) = 0.368, P = 0.0001; BPuwr: R(2) = 0.300, P = 0.0008). Weighted registration improves accuracy of binding potential estimates and may be a promising approach to enhance the diagnostic outcome of SPECT imaging, correlation with disease severity, and for monitoring disease progression in Parkinsonian syndromes.

Microalbuminuria predicts silent myocardial ischaemia in type 2 diabetes patients.

PURPOSE: Myocardial ischaemia is frequently silent in patients with type 2 diabetes. Although it has been proposed as a potential screening tool, the role of myocardial perfusion single photon emission computed tomography (MPS) has recently been questioned, due to the low prevalence of positive scans and the low rate of cardiac events. The aim of this study was to assess if pretest clinical variables can identify a subgroup of asymptomatic patients with type 2 diabetes at risk of silent myocardial ischaemia and a subsequent poor outcome METHODS: This prospective study included 77 patients (50 men, mean age 63 ± 9 years) with type 2 diabetes and no known coronary artery disease (CAD) or angina pectoris who underwent gated MPS to screen for CAD between March 2006 and October 2008. MPS images were interpreted using a semiquantitative visual 20-segment model to define summed stress, rest and difference scores. Ischaemia was defined as a sum difference score (SDS) ≥2. Patients were followed-up (median 4.1 years, range 0.8 - 6.1 years) and cardiac hard events (cardiac death or nonfatal myocardial infarction) were recorded. RESULTS: Silent ischaemia was detected in 25 of the 77 patients (32 %). Specifically, 10 patients (13 %) had mild ischaemia (SDS 2 to ≤4) and 15 patients (19 %) had severe ischaemia (SDS >4). In univariate binary logistic analysis, microalbuminuria was the only significant predictor of silent ischaemia on MPS (odds ratio 4.42, 95 % CI 1.27 - 15.40; P = 0.019). The overall accuracy of microalbuminuria for predicting silent ischaemia was 71.4 % and was 89.6 % for predicting severe ischaemia. Kaplan-Meier curves showed no significant group differences in 5-year cardiac event-free survival between patients with and those without microalbuminuria, or between patients with SDS ≥2 and those with SDS <2. In contrast, 5-year event-free survival was significantly lower in patients with SDS >4 than in patients with SDS ≤4: 55.6 % (95 % CI 39.0 - 72.2 %) vs. 94.5 % (95 % CI: 91.4 - 97.6 %), respectively (Breslow test, chi-square 20.9, P < 0.001). Median cardiac event-free survival was not observed in the whole group, while the 25th percentile of cardiac event-free survival was reached only in patients with SDS >4 (2.3 years). In univariate Cox regression analysis, SDS >4 predicted cardiac event-free survival (hazard ratio 12.87, 95 % CI 2.86 - 27.98; P = 0.001), while SDS ≥2 did not (hazard ratio 2.78, 95 % CI 0.62 - 12.46, P = 0.16). CONCLUSION: In this group of patients with type 2 diabetes, microalbuminuria was the only predictor of silent ischaemia on MPS. Assessment of microalbuminuria should be routinely considered among the first risk stratification steps for CAD in patients with type 2 diabetes, even though severe ischaemia on MPS is a major predictor of cardiac event-free survival.

Brain metabolic correlates of Locus Coeruleus degeneration in Alzheimer's disease: a multimodal neuroimaging study.

Locus Coeruleus (LC) degeneration occurs early in Alzheimer's disease (AD) and this could affect several brain regions innervated by LC noradrenergic axon terminals, as these bear neuroprotective effects and modulate neurovascular coupling/neuronal activity. We used LC-sensitive Magnetic Resonance imaging (MRI) sequences enabling LC integrity quantification, and [18F]Fluorodeoxyglucose (FDG) PET, to investigate the association of LC-MRI changes with brain glucose metabolism in cognitively impaired patients (30 amnesticMCI and 13 demented ones). Fifteen cognitively intact age-matched controls (HCs) were submitted only to LC-MRI for comparison with patients. Voxel-wise regression analyses of [18F]FDG images were conducted using the LC-MRI parameters signal intensity (LCCR) and LC-belonging voxels (LCVOX). Both LCCR and LCVOX were significantly lower in patients compared to HCs, and were directly associated with [18F]FDG uptake in fronto-parietal cortical areas, mainly involving the left hemisphere (p < 0.001, kE > 100). These results suggest a possible association between LC degeneration and cortical hypometabolism in degenerative cognitive impairment with a prevalent left-hemispheric vulnerability, and that LC degeneration might be linked to large-scale functional network alteration in AD pathology.