Absence Of Uptake Research Articles

Vital Dye Uptake of YO-PRO-1 and DASPEI Depends Upon Mechanoelectrical Transduction Function in Zebrafish Hair Cells.

Vital dyes allow the visualization of cells in vivo without causing tissue damage, making them a useful tool for studying lateral line and inner ear hair cells in living zebrafish and other vertebrates. FM1-43, YO-PRO-1, and DASPEI are three vital dyes commonly used for hair cell visualization. While it has been established that FM1-43 enters hair cells of zebrafish and other organisms through the mechanoelectrical transduction (MET) channel, the mechanism of entry into hair cells for YO-PRO-1 and DASPEI has not been established despite widespread use. We hypothesize that YO-PRO-1 and DASPEI entry into zebrafish hair cells is MET channel uptake dependent similar to FM1-43. To test this hypothesis, we used both genetic and pharmacologic means to block MET channel function. Genetic based MET channel assays were conducted with two different mechanotransduction defective zebrafish lines, specifically the myo7aa-/- loss of function mutant tc320b (p.Y846X) and cdh23-/- loss of function mutant (c.570-571del). Pharmacologic assays were performed with Gadolinium(III) Chloride (Gad(III)), a compound that can temporarily block mechanotransduction activity. Five-day post fertilization (5dpf) myo7aa-/- and cdh23-/- larvae incubated with FM1-43, YO-PRO-1, and DASPEI all showed nearly absent uptake of each vital dye. Treatment of wildtype zebrafish larvae with Gad(III) significantly reduces uptake of FM1-43, YO-PRO-1, and DASPEI vital dyes. These results indicate that YO-PRO-1 and DASPEI entry into zebrafish hair cells is MET channel dependent similar to FM1-43. This knowledge expands the repertoire of vital dyes that can be used to assess mechanotransduction and MET channel function in zebrafish and other vertebrate models of hair cell function.

Application of Dynamic [18F]FDG PET/CT Multiparametric Imaging Leads to an Improved Differentiation of Benign and Malignant Lung Lesions.

To evaluate the potential of whole-body dynamic (WBD) 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) multiparametric imaging in the differential diagnosis between benign and malignant lung lesions. We retrospectively analyzed WBD PET/CT scans from patients with lung lesions performed between April 2020 and March 2023. Multiparametric images including standardized uptake value (SUV), metabolic rate (MRFDG) and distribution volume (DVFDG) were visually interpreted and compared. We adopted SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG) for semi-quantitative analysis, MRmax and DVmax values for quantitative analysis. We also collected the patients' clinical characteristics. The variables above with P-value < 0.05 in the univariate analysis were entered into a multivariate logistic regression. The statistically significant metrics were plotted on receiver-operating characteristic (ROC) curves. A total of 60 patients were included for data evaluation. We found that most malignant lesions showed high uptake on MRFDG and SUV images, and low or absent uptake on DVFDG images, while benign lesions showed low uptake on MRFDG images and high uptake on DVFDG images. Most malignant lesions showed a characteristic pattern of gradually increasing FDG uptake, whereas benign lesions presented an initial rise with rapid fall, then kept stable at a low level. The AUC values of MRmax and SUVmax are 0.874 (95% CI: 0.763-0.946) and 0.792 (95% CI: 0.667-0.886), respectively. DeLong's test showed the difference between the areas is statistically significant (P < 0.001). Our study demonstrated that dynamic [18F]FDG PET/CT imaging based on the Patlak analysis was a more accurate method of distinguishing malignancies from benign lesions than conventional static PET/CT scans.

A case of struma ovarii with coexistent Brenner tumor presenting with thyrotoxicosis

ABSTRACT Struma ovarii is an ovarian tumor, characterized by the presence of thyroid tissue comprising &gt;50% of the overall mass. Although struma ovarii does not usually secrete thyroid hormones, there are cases in which it produces thyroid hormones, which results in hyperthyroidism. Here, we report the case of a 73-year-old female who presented with a right ovarian mass and symptoms suggestive of thyrotoxicosis. Her thyroid function test showed suppressed thyroid-stimulating hormone and elevated T3 and T4 levels. We suspected thyroiditis initially. Later, in view of persistent thyrotoxicosis, she was started on antithyroid drugs. Tc99 pertechnetate thyroid uptake scan showed absent uptake in the neck. A possibility of struma ovarii was considered. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. Histopathology revealed &gt;80% thyroid tissue suggestive of struma ovarii with a coexistent Brenner tumor. Postoperatively, her thyrotoxicosis got resolved. To conclude, in any case of thyrotoxicosis that is persisting and with absent uptake in the neck, rare cases such as struma ovarii should be considered. Struma ovarii with a coexistent Brenner tumor is a very rare finding.

Radioactive iodine refractoriness in Middle Eastern differentiated thyroid cancer: clinical outcome and risk factor analysis.

Radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) has received increasing attention due to its poor prognosis. However, outcomes may vary among patients with RAIR-DTC. The role of clinico-pathological and molecular prognostic factors in survival remains controversial, resulting in difficulty in selecting patients for new targeted therapies. We assessed mortality rate and DTC-specific survival in Middle Eastern RAIR-DTC to identify prognostic factors associated with survival. This single center, retrospective study enrolled 268 patients with RAIR-DTC. Mortality rate and DTC-specific survival were analyzed to identify prognostic factors related to survival. Univariate and multivariate analysis were performed using Cox proportional hazards model. Of the 268 cases of RAIR-DTC, 40.3% (108/268) had absent 131I uptake (either on diagnostic or post-therapy whole body scan), 15.3% (41/268) had progressive disease (PD) despite 131I, 7.5% (20/268) had persistent disease despite cumulative activity of I131 of >600 mCi and 36.9% (n=99/268) developed distant metastasis. On multivariate analysis, age (more than 45 years), presence of metastatic disease and tumors harboring telomerase reverse transcriptase (TERT) promoter mutations were independent prognostic factors for poor DTC-specific survival. Subjects were divided into 3 groups according to the number of risk factors; low risk (no risk factors); intermediate (≤ 2 risk factors); and high risk (all the 3 risk factors). Ten-year DTC-specific survival rates in low, intermediate and high-risk groups were 100.0%, 92.9% and 53.6%, respectively. The contribution of age greater than 45 years to RAIR-DTC mortality is impactful. Older age, presence of distant metastasis and TERT mutations could be used as early predictors of RAIR-DTC cases. The identification of prognostic factors for poor survival in RAIR-DTC may improve the selection of patients for more personalized surveillance and therapeutic modalities.

FAPi-Based Agents in Thyroid Cancer: A New Step towards Diagnosis and Therapy? A Systematic Review of the Literature.

(1) Background: Thyroid cancer (TC) is often treated with surgery followed by iodine-131. Up to 50% of the instances of TC lose their avidity to 131I, becoming more aggressive. In this scenario, [18F]FDG PET/CT imaging is used for evaluating the widespread nature of the disease, despite its low sensitivity and a false negative rate of 8-21.1%. A novel class of PET agents targeting the fibroblast activation protein inhibitor (FAPi) has emerged, studied particularly for their potential application to theranostics. (2) Methods: A search of the literature was performed by two independent authors (P.G. and L.E.) using the PubMed, Scopus, Web of Science, Cochrane Library, and EMBASE databases. The following terms were used: "FAP" or "FAPi" or "Fibroblast activating protein" and "thyroid" or "thyroid cancer", in different combinations. The included papers were original articles, clinical studies, and case reports in the English language. No time limits were used. Editorials, conference papers, reviews, and preclinical studies were excluded. (3) Results: There were 31 papers that were selected. Some studies reported a low or absent FAPi uptake in TC lesions; others reported promising findings for the detection of metastases. (4) Conclusions: The preliminary results are encouraging. FAPI agents are an alternative to [18F]FDG and a promising theranostic tool. However, further studies with a larger population are needed.

Clinical and Prognostic Implications of Right Ventricular Uptake on Bone Scintigraphy in Transthyretin Amyloid Cardiomyopathy.

The extent of myocardial bone tracer uptake with technetium pyrophosphate, hydroxymethylene diphosphonate, and 3,3-diphosphono-1,2-propanodicarboxylate in transthyretin amyloid cardiomyopathy (ATTR-CM) might reflect cardiac amyloid burden and be associated with outcome. Consecutive patients with ATTR-CM who underwent diagnostic bone tracer scintigraphy with acquisition of whole-body planar and cardiac single-photon emission computed tomography (SPECT) images from the National Amyloidosis Centre and 4 Italian centers were included. Cardiac uptake was defined according to the Perugini classification: 0=absent cardiac uptake; 1=mild uptake less than bone; 2=moderate uptake equal to bone; and 3=high uptake greater than bone. Extent of right ventricular (RV) uptake was defined as focal (basal segment of the RV free wall only) or diffuse (extending beyond basal segment) on the basis of SPECT imaging. The primary outcome was all-cause mortality. Among 1422 patients with ATTR-CM, RV uptake accompanying left ventricular uptake was identified by SPECT imaging in 100% of cases at diagnosis. Median follow-up in the whole cohort was 34 months (interquartile range, 21 to 50 months), and 494 patients died. By Kaplan-Meier analysis, diffuse RV uptake on SPECT imaging (n=936) was associated with higher all-cause mortality compared with focal (n=486) RV uptake (77.9% versus 22.1%; P<0.001), whereas Perugini grade was not associated with survival (P=0.27 in grade 2 versus grade 3). On multivariable analysis, after adjustment for age at diagnosis (hazard ratio [HR], 1.03 [95% CI, 1.02-1.04]; P<0.001), presence of the p.(V142I) TTR variant (HR, 1.42 [95% CI, 1.20-1.81]; P=0.004), National Amyloidosis Centre stage (each category, P<0.001), stroke volume index (HR, 0.99 [95% CI, 0.97-0.99]; P=0.043), E/e' (HR, 1.02 [95% CI, 1.007-1.03]; P=0.004), right atrial area index (HR, 1.05 [95% CI, 1.02-1.08]; P=0.001), and left ventricular global longitudinal strain (HR, 1.06 [95% CI, 1.03-1.09]; P<0.001), diffuse RV uptake on SPECT imaging (HR, 1.60 [95% CI, 1.26-2.04]; P<0.001) remained an independent predictor of all-cause mortality. The prognostic value of diffuse RV uptake was maintained across each National Amyloidosis Centre stage and in both wild-type and hereditary ATTR-CM (P<0.001 and P=0.02, respectively). Diffuse RV uptake of bone tracer on SPECT imaging is associated with poor outcomes in patients with ATTR-CM and is an independent prognostic marker at diagnosis.

Shining a Light on Hidden Thyroids: A Case Exploring the Potential of Technetium Imaging for Lingual Thyroid Diagnosis

Ectopic thyroid, the presence of thyroid tissue in locations other than the normal anterior neck region between the second and fourth tracheal cartilages, is the most common form of thyroid dysgenesis. A 32-year-old female patient sought medical attention at the Otolaryngology Department with a foreign body sensation in her throat. To ensure an accurate diagnosis, hereby, the authors conducted a comprehensive diagnostic work-up, which included Technetium-99 (Tc-99m) scanning. Remarkably, the scanning results revealed radiotracer uptake in the base of the tongue while indicating an absence of uptake in the thyroid bed. By shedding light on present captivating case, the present report offers valuable insights into the usage of Technetium imaging in diagnosing doubtful Lingual Thyroid (LT) cases.

Clinical red flags associated with transthyretin amyloid cardiomyopathy in patients with left ventricular hypertrophy: results of the TTRACK study

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a life-threatening, systemic disorder that results in progressive physical disability, substantially reduced quality of life, and high morbidity and mortality rates. ATTR-CM is an underrecognized cause of increased left ventricular (LV) wall thickness in older adults, and delayed diagnosis can lead to worse clinical outcomes. To facilitate early identification of patients with LV hypertrophy (LVH) at risk for ATTR-CM, greater recognition of diagnostic ‘red flags’ is required. Purpose To determine the association between diagnostic red flags and ATTR-CM in patients with LVH. Methods TTRACK is a multicentre, non-interventional epidemiological study (ClinicalTrials.gov: NCT03842163). Eligible patients were ≥50 years of age and had unexplained LVH (LV maximum wall thickness ≥15 mm [echocardiogram]). After undergoing technetium-99m-DPD/-PYP/-HMDP-labelled bone scintigraphy, scans were categorized by the degree of tracer uptake in the heart; Perugini grades 0, 1, 2 and 3 represented absent, low, moderate and high uptake, respectively. Immunofixation electrophoresis was used to detect monoclonal protein abnormalities; grade 2 and 3 scans without evidence of monoclonal gammopathy were considered diagnostic for ATTR-CM. The frequency of predetermined clinical disease markers was compared in patients without monoclonal protein abnormalities and grade 0 or grade 2/3 scans. Results Of 766 eligible patients with scintigraphy data, 521 (68.0%) had grade 0 cardiac uptake; 37 (4.8%) had grade 1; and 208 (27.2%) had grade 2/3. Among patients with moderate/high uptake, 137 (65.9% of those with grade 2/3 uptake; 17.9% of the overall cohort) had no monoclonal protein abnormalities (ATTR-CM); 56 (26.9%) had monoclonal gammopathy of undetermined significance or light chain amyloidosis; and 15 (7.2%) patients had unknown monoclonal test findings. On univariable analysis, carpal tunnel syndrome (odds ratio [95% CI], 27.7 [16.7, 46.1]), permanent atrial fibrillation (3.4 [2.2, 5.2]), male sex (2.9 [1.8, 4.8]) and advanced heart failure (1.8 [1.2, 2.9]) were the strongest predictors for grade 2/3 scans; on multivariable analysis, carpal tunnel syndrome (50.3 [23.4, 108.0]), male sex (9.1 [3.9, 21.3] and age (1.7 [1.4, 2.1]) were the strongest predictors (Figure). Conclusions In the TTRACK study, 18% of patients ≥50 years of age with unexplained LVH ≥15 mm had ATTR-CM. Carpal tunnel syndrome, male sex and advanced age were associated with a greater likelihood of ATTR-CM.

Temporal Changes in Coronary 18F-Fluoride Plaque Uptake in Patients with Coronary Atherosclerosis.

Coronary 18F-sodium fluoride (18F-fluoride) uptake is a marker of both atherosclerotic disease activity and disease progression. It is currently unknown whether there are rapid temporal changes in coronary 18F-fluoride uptake and whether these are more marked in those with clinically unstable coronary artery disease. This study aimed to determine the natural history of coronary 18F-fluoride uptake over 12 mo in patients with either advanced chronic coronary artery disease or a recent myocardial infarction. Methods: Patients with established multivessel coronary artery disease and either chronic disease or a recent acute myocardial infarction underwent coronary 18F-fluoride PET and CT angiography, which was repeated at 3, 6, or 12 mo. Coronary 18F-fluoride uptake was assessed in each vessel by measuring the coronary microcalcification activity (CMA). Coronary calcification was quantified by measuring calcium score, mass, and volume. Results: Fifty-nine patients had chronic coronary artery disease (median age, 68 y; 93% male), and 52 patients had a recent myocardial infarction (median age, 65 y; 83% male). Reflecting the greater burden of coronary artery disease, baseline CMA values were higher in those with chronic coronary artery disease. Coronary 18F-fluoride uptake (CMA > 0) was associated with higher baseline calcium scores (294 Agatston units [AU] [interquartile range, 116-483 AU] vs. 72 AU [interquartile range, 8-222 AU]; P < 0.001) and more rapid progression of coronary calcification scores (39 AU [interquartile range, 10-82 AU] vs. 12 AU [interquartile range, 1-36 AU]; P < 0.001) than was the absence of uptake (CMA = 0). Coronary 18F-fluoride uptake did not markedly alter over the course of 3, 6, or 12 mo in patients with either chronic coronary artery disease or a recent myocardial infarction. Conclusion: Coronary 18F-fluoride uptake is associated with the severity and progression of coronary artery disease but does not undergo a rapid dynamic change in patients with chronic or unstable coronary artery disease. This finding suggests that coronary 18F-fluoride uptake is a temporally stable marker of established and progressive disease.

Comparative prognostic utility of visual grade and heart-to-contralateral lung ratio in patients undergoing 99mTc-pyrophosphate radiotracer cardiac scintigraphy

Abstract Introduction Transthyretin (ATTR) cardiac amyloidosis (CA) is an underdiagnosed form of restrictive cardiomyopathy leading to a rapid progression into heart failure. 99mTc-labeled radiotracer cardiac scintigraphy is crucial for the evaluation of CA. Semiquantitative (Perugini visual grade) and quantitative (heart-to-contralateral lung ratio, H/CL) parameters are used to assessing CA via cardiac scintigraphy. Purpose We aimed to assess the comparative prognostic utility of the Perugini visual grade and heart to contralateral lung ratio. Methods The study population was identified based on an institutional registry of consecutive patients undergoing 99mTc-PYP radiotracer cardiac scintigraphy for suspected CA between January 2020-October 2021. The H/CL is calculated by the fraction of heart region of interest (ROI) mean uptake counts to the contralateral chest ROI. The visual scoring system compares uptake between bone (rib) and heart where 0 = absent cardiac uptake, 1 = uptake less than bone, 2 = uptake equal to bone, and 3 = is uptake greater than bone. Ejection fraction (EF) was obtained from echocardiographic studies done around the time of cardiac scintigraphy. MACE was defined as a composite of inclusive of all-cause death, myocardial infarction, admission for heart failure and late revascularization – percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) &amp;gt;90 days after imaging. Results A total of 330 patients (mean age 70.9±12.2 years, 62.2% male) were included in the analysis. Risk factors were prevalent (59.7% hypertension, Heart Failure 68.3%, 26.5% dyslipidemia, 26.2% diabetes) (Table 1). In total, 32.6% of the cohort had studies suggestive of ATTR CA. Median time between echocardiography and cardiac scintigraphy was 7 days (IQR 5–42 days). A higher frequency of MACE was reported in patients with a 2+ visual grade (30% vs 42%, p=0.03). A H/CL &amp;gt;1.5 was associated with borderline significance (43% vs 35% p=0.07). Conclusion Our analysis showed that the Perugini visual grading of transthyretin cardiac amyloidosis conferred the best prognostic utility contrary to heart to contralateral lung ratio in 99mTc-PYP radiotracer cardiac scintigraphy. Funding Acknowledgement Type of funding sources: None.

Correlation of Target Volumes on Magnetic Resonance Imaging and Prostate-Specific Membrane Antigen Brain Scans in the Treatment Planning of Glioblastomas.

Imaging of gliomas/glioblastomas has always been challenging. Many magnetic resonance imaging (MRI) techniques are available for imaging glioblastomas. MRI cannot always differentiate tumor from nonspecific changes and postoperative changes in brain tissue. Among the new positron emission tomography-computed tomography (PET-CT) tracers, gallium-68 prostate-specific membrane antigen (Ga-68 PSMA-11 PET-CT) appears to be the most promising one. The absence of uptake by normal brain parenchyma leads to high tumor-to-background ratio leading to better visualization of the tumor. The aim of this study was to assess the correlation of target volumes on MRI and PSMA brain scans in the treatment planning of glioblastomas. Twenty-four patients in the age group of 5-75 years with histologically proven glioblastoma were included in the study following maximum safe resection. Simulation for treatment planning was done with Ga-68 PSMA PET-CT brain with IV iodine-based contrast. The pre- and postoperative MRI images were fused with PSMA simulation images. Gross tumor volumes (GTVs) contoured on T1-contrast MRI and on PSMA scans were compared. GTV contoured on MRI and PSMA brain scans showed complete overlap in 17 patients. In seven patients, the target volumes drawn on Ga-68 PSMA brain scans were slightly smaller than the target volumes drawn on MRI brain scans. This difference in volumes could be due to postoperative changes which showed enhancement on the MRI scan. Ga-68 PSMA PET-CT shows good correlation with MRI brain in the evaluation and RT planning in glioblastomas. Tumor necrosis and postoperative changes did not show PSMA uptake. Precise target delineation on PSMA PET-CT can potentially result in smaller and more accurate GTVs, which in turn would result in less RT-induced side effects.

Blanching Defects at the Pressure Points: Observations from Dynamic Total-Body PET/CT Studies.

Total-body PET/CT allows simultaneous acquisition of all the body parts in a single bed position during the radiotracer uptake phase. Dynamic imaging protocols employing total-body PET could demonstrate findings that may not have been previously visualized or described using conventional PET/CT scanners. We examined the characteristics of blanching defects, areas of markedly reduced (partial defect) or absent (complete defect) radiotracer uptake seen at the skin/subcutaneous tissues opposite the bony prominences at pressure points. Methods: In this observational study, 77 participants underwent dynamic total-body PET/CT imaging using 18F-FDG (Group 1, N = 47, 60-min dynamic, arms-down, divided into 3 subgroups according to the injected dose) or 18F-fluciclovine (Group 2, N = 30, 25-min dynamic, arms above the head). 40 out of 47 participants in Group 1 were re-imaged at 90 min after being allowed off the scanning table. Blanching defects, partial or complete, were characterized opposite the bony prominences at 7 pressure points (the skull, scapula, and calcaneus bilaterally, as well as the sacrum). Association of the blanching defects with different clinical and technical characteristics were analyzed using uni- and multi-variate analyses. Results: A total of 124 blanching defects were seen in 68 out of 77 (88%) participants at one or more pressure points. Blanching defects were higher, on average, in Group 2 participants (3.5±1.7) compared to Group 1 (2.1±1.4; P <0.001), but it did not vary within Group 1 for different 18F-FDG dose subgroups. All defects resumed normal pattern on delayed static (90-min) images except for 14 partial defects. No complete blanching defects were seen on the 90-min images. By multivariate analysis, arm positioning above the head was associated with skull defects; scapular and sacral defects were significantly more encountered in men and with lower BMI, while calcaneal defects could not be associated to any factor. Conclusion: Blanching defects opposite the bony pressure points are common on dynamic total-body PET/CT images using different radiopharmaceuticals and injection doses. Their appearance should not be immediately interpreted as an abnormality. The current findings warrant further exploration in a prospective setting and may be utilized to study various mechano-pathologic conditions, such as pressure ulcers.

Cardiac sympathetic innervation in Parkinson\u2019s disease versus multiple system atrophy

PurposeThe aims of this study were to evaluate the diagnostic accuracy of the dual imaging method combining cardiac iodine-123-metaiodobenzylguanidine single-photon emission computed tomography combined with low-dose chest computed tomography compared to routine cardiac scintigraphy, and assess regional differences in tracer distribution and the relationships between imaging and autonomic function in Parkinson’s disease and multiple system atrophy.MethodsA prospective study including 19 Parkinson’s disease and 12 multiple system atrophy patients was performed. Patients underwent clinical evaluation, iodine-123-metaiodobenzylguanidine single-photon emission computed tomography combined with chest computed tomography, planar scintigraphy, and cardiovascular autonomic function tests.ResultsCo-registration of single-photon emission computed tomography and chest computed tomography resulted in three groups with distinct patterns of tracer uptake: homogeneous, non-homogeneously reduced and absent. There was a significant difference in group allocation among patients with multiple system atrophy and Parkinson’s disease (p = 0.001). Most multiple system atrophy patients showed homogeneous uptake, and the majority of Parkinson’s disease patients showed absent cardiac tracer uptake. We identified a pattern of heterogeneous cardiac tracer uptake in both diseases with reductions in the apex and the lateral myocardial wall. Sympathetic dysfunction reflected by a missing blood pressure overshoot during Valsalva manoeuvre correlated with cardiac tracer distribution in Parkinson’s disease patients (p < 0.001).ConclusionsThe diagnostic accuracy of the dual imaging method and routine cardiac scintigraphy were similar. Anatomical tracer allocation provided by the dual imaging method of cardiac iodine-123-metaiodobenzylguanidine single-photon emission computed tomography and chest computed tomography identified a heterogeneous subgroup of Parkinson’s disease and multiple system atrophy patients with reduced cardiac tracer uptake in the apex and the lateral wall. Sympathetic dysfunction correlated with cardiac imaging in Parkinson’s disease patients.

Glycoprotein IIb/IIIa receptor targeted PET/CT imaging: a novel diagnostic tool for detecting bioprosthetic valve thrombosis

Abstract Background/Introduction Bioprosthetic valve thrombosis (BPVT) is an important clinical entity eventually following both bioprosthetic surgical and transcatheter aortic valve replacement. Although dynamic contrast-enhanced 4D-MDCT has improved the diagnosis of BPVT, more sensitive and pathology-specific non-invasive imaging tools are lacking. Recently, the glycoprotein IIb/IIIa receptor targeted, elarofiban-derived PET/CT imaging radiotracer [18F]GP1 has been successfully used for visualization of acute venous and arterial thrombi. Purpose We hypothesized that [18F]GP1 PET/CT imaging is suitable to detect BPVT. Methods In this proof-of-concept study, patients after bioprosthetic aortic valve replacement with symptomatic, severe hemodynamic valve dysfunction and confirmed hypoattenuated leaflet thickening (HALT) in dynamic 4D-MDCT were offered to participate in compassionate use examinations to undergo PET/CT imaging with the investigational [18F]GP1 PET tracer at baseline and after a 12-week course of therapeutic oral anticoagulation. Results This case series reports on three patients after aortic valve replacement. Two patients with symptomatic, obstructive BPVT as confirmed by echocardiography and 4D-MDCT fulfilled specified criteria and underwent [18F]GP1 PET/CT imaging. [18F]GP1 PET/CT clearly distinguished between blood pool activity and thrombotic foci. Clot-to-blood ratios at baseline were 8.2 and 4.5, respectively. A 12-week trial of therapeutic oral anticoagulation was associated with a regression of mean transprosthetic pressure gradient and reversal of HALT. Follow-up 4D-MDCT corroborated thrombus resolution in both patients. Correspondingly, [18F]GP1 PET/CT imaging demonstrated decreased tracer uptake in both patients. Clot-to-blood ratio at follow-up visit decreased to 1.2 and 2.9, respectively. While absent tracer uptake was seen in patient #1, residual tracer uptake was observed in patient #2 suggestive of ongoing platelet aggregation. One asymptomatic SAVR patient was examined with [18F]GP1 PET/CT for a different compassionate use and no thrombotic foci were detected on the leaflets. Conclusions [18F]GP1 PET/CT is a novel imaging technique in patients with obstructive BPVT. In a head-to-head comparison we show that [18F]GP1 PET/CT may have incremental diagnostic value over dynamic contrast-enhanced 4D-MDCT alone by detection of sites of ongoing platelet aggregation at the molecular level. [18F]GP1 PET/CT may serve as a novel, highly sensitive tool to overcome some limitations of current diagnostic imaging modalities for detecting BPVT and may prove useful for the monitoring and guidance of therapeutic interventions. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Life Molecular Imaging provided material for [18F]GP1 radiolabeling free of charge as part of an ongoing research collaboration.

Utility of 18F-FDG PET/CT in Management of Pancreatic and Periampullary Masses-Prospective Study from a Tertiary Care Center.

Characterizing a pancreatic or periampullary mass lesion as benign or malignant on conventional imaging is difficult due to overlapping morphological features. 18F-FDG PET/CT is a molecular imaging technique with reportedly higher sensitivity and specificity in the differentiation of benign and malignant pancreatic and periampullary masses. In this prospective study, we evaluated the utility of 18F-FDG PET/CT in patients with recently diagnosed pancreatic and periampullary masses. Based on FDG uptake pattern, diffuse or absent uptake was considered benign and focal increased uptake as malignant. Among the 32 patients included in the study, pathological examination confirmed 25 as positive for malignancy and the remaining 7 as benign etiology. Based on FDG uptake pattern, sensitivity, specificity, PPV, NPV, and accuracy of the study were 92%, 42.8%, 85.2%, 60%, and 81.3% respectively. 18F-FDG PET/CT had a statistically significant higher detection rate in the evaluation of regional lymph nodes and distant organ metastases compared to radiological imaging. In 7/25 (14%) malignant cases, 18F-FDG PET/CT detected additional distant metastases which were not detected by conventional imaging and thus resulting in change in management from curative resection to palliative therapy. To conculde, 18F-FDG PET/CT uptake pattern can characterize pancreatic and periampullary masses as benign or malignant with a relatively good accuracy. Using 18F-FDG PET/CT for initial staging of pancreatic and periampullary cancer helps in appropriate staging and optimal selection of treatment modality compared to conventional imaging techniques.

Characterizing omental PET/CT findings for differentiating tuberculous peritonitis from peritoneal carcinomatosis.

To characterize and investigate PET/CT findings in the omentum in the differentiation of tuberculous peritonitis (TBP) and peritoneal carcinoma (PC). Thirty-nine patients with TBP and 113 patients with PC who underwent PET/CT were retrospectively enrolled. The omental uptake intensity, distribution characteristics, contracture, size and boundary of soft-tissue lesions, and CT patterns were reviewed. Absent and focal FDG uptake in the lesser omentum was more common in the PC patients (P = 0.034 and P = 0.017, respectively), and diffuse FDG uptake in the lesser omentum was more common in the TBP patients (P < 0.001). An apron-like pattern in the greater omentum commonly occurred in the TBP patients (P = 0.004). Micronodules (< 5mm) were more common in the TBP patients (P < 0.001), and masses (> 3cm) were more common in the PC patients (P = 0.001). Smudged and nodular patterns occurred more frequently in the TBP patients than in the PC patients (P < 0.001 and P = 0.003, respectively), and the caked pattern occurred more frequently in the PC patients (P < 0.001). There was no significant difference in the FDG uptake intensity and the boundary of soft-tissue lesions between the TBP and PC patients (P = 0.191 and P = 0.061, respectively). Diffuse FDG uptake, an apron-like pattern, micronodules, and a smudged and nodular pattern might be significant differential features of TBP. Absent and/or focal FDG uptake, mass, and a caked pattern might be significant differential features of PC.

Optimizing Cord Blood Thyroid Stimulating Hormone Cutoff for Screening of Congenital Hypothyroidism-Experience from Screening 164,000 Newborns in a Tertiary Hospital in India.

Background and Objectives:In our institution, we have an ongoing newborn thyroid screening (NBS) program since July 2001. In the initial 9 months, we used cord blood thyroid-stimulating hormone (TSH) (CBTSH) cutoff of 20 mIU/L and thereafter the cutoff was increased to 25 mIU/L. Our objective was to evaluate whether a CBTSH cutoff of 25 mIU/L is sensitive and cost-effective in NBS of congenital hypothyroidism (CH).Materials and Methods:All in-born babies are screened and those with CBTSH ≥25 mIU/L are recalled for confirmatory TSH/T4/FT4 tests. CH is confirmed with elevated TSH and low T4/FT4. Those with CBTSH 20–24.99 mIU/L were recalled for confirmatory tests in initial period of our NBS and prospectively between January and August 2017. Statistical analysis was done to derive positive predictive value and sensitivity to diagnose CH for each CBTSH between 20 and 30 mIU/L.Results:A total of 164,163 neonates were screened from July 2001 to August 2017. Of the 2352 babies with CBTSH ≥25–30 mIU/L, 1763 returned for retesting and 5 confirmed as CH (4 gland-in-situ and 1 absent uptake on nuclear scan). Of the 14,742 screened during the study period, 195 of the 293 babies with CBTSH 20–24.99 mIU/L returned for retesting and none diagnosed as CH. A CBTSH of 25 mIU/L has 99.2% sensitivity and 97.5% specificity. A lower screen TSH cutoff 20 mIU/L would result in recall of additional 300 babies/year with no definite improvement in sensitivity.Conclusions:Our data justify the continuation of using screen TSH cutoff of 25 mIU/L while using cord blood for NBS in our population. With a diverse and large population, it is important that we use feasible regional screen cutoffs for optimal use of our resources.

Infants Diagnosed with Athyreosis on Scintigraphy May Have a Gland Present on Ultrasound and Have Transient Congenital Hypothyroidism

Scintigraphy using technetium-99m (^99mTc) is the gold standard for imaging the thyroid gland in infants with congenital hypothyroidism (CHT) and is the most reliable method of diagnosing an ectopic thyroid gland. One of the limitations of scintigraphy is the possibility that no uptake is detected despite the presence of thyroid tissue, leading to the spurious diagnosis of athyreosis. Thyroid ultrasound is a useful adjunct to detect thyroid tissue in the absence of ^99mTc uptake. Aims: We aimed to describe the incidence of sonographically detectable in situ thyroid glands in infants scintigraphically diagnosed with athyreosis using ^99mTc and to describe the clinical characteristics and natural history in these infants. Methods: The newborn screening records of all infants diagnosed with CHT between 2007 and 2016 were reviewed. Those diagnosed with CHT and athyreosis confirmed on scintigraphy were invited to attend a thyroid ultrasound. Results: Of the 488 infants diagnosed with CHT during the study period, 18/73 (24.6%) infants with absent uptake on scintigraphy had thyroid tissue visualised on ultrasound (3 hypoplastic thyroid glands and 15 eutopic glands). The median serum thyroid-stimulating hormone (TSH) concentration at diagnosis was significantly lower than that in infants with confirmed athyreosis (no gland on ultrasound and no uptake on scintigraphy) (74 vs. 270 mU/L), and median free T4 concentration at diagnosis was higher (11.9 vs. 3.9 pmol/L). Six of 10 (60%) infants with no uptake on scintigraphy but a eutopic gland on ultrasound had transient CHT. Conclusion: Absent uptake on scintigraphy in infants with CHT does not rule out a eutopic gland, especially in infants with less elevated TSH concentrations. Clinically, adding thyroid ultrasound to the diagnostic evaluation of infants who have athyreosis on scintigraphy may avoid committing some infants with presumed athyreosis to lifelong levothyroxine treatment.

Positron emission tomography and magnetic resonance imaging in experimental human malaria to identify organ-specific changes in morphology and glucose metabolism: A prospective cohort study.

Plasmodium vivax has been proposed to infect and replicate in the human spleen and bone marrow. Compared to Plasmodium falciparum, which is known to undergo microvascular tissue sequestration, little is known about the behavior of P. vivax outside of the circulating compartment. This may be due in part to difficulties in studying parasite location and activity in life. To identify organ-specific changes during the early stages of P. vivax infection, we performed 18-F fluorodeoxyglucose (FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) at baseline and just prior to onset of clinical illness in P. vivax experimentally induced blood-stage malaria (IBSM) and compared findings to P. falciparum IBSM. Seven healthy, malaria-naive participants were enrolled from 3 IBSM trials: NCT02867059, ACTRN12616000174482, and ACTRN12619001085167. Imaging took place between 2016 and 2019 at the Herston Imaging Research Facility, Australia. Postinoculation imaging was performed after a median of 9 days in both species (n = 3 P. vivax; n = 4 P. falciparum). All participants were aged between 19 and 23 years, and 6/7 were male. Splenic volume (P. vivax: +28.8% [confidence interval (CI) +10.3% to +57.3%], P. falciparum: +22.9 [CI -15.3% to +61.1%]) and radiotracer uptake (P. vivax: +15.5% [CI -0.7% to +31.7%], P. falciparum: +5.5% [CI +1.4% to +9.6%]) increased following infection with each species, but more so in P. vivax infection (volume: p = 0.72, radiotracer uptake: p = 0.036). There was no change in FDG uptake in the bone marrow (P. vivax: +4.6% [CI -15.9% to +25.0%], P. falciparum: +3.2% [CI -3.2% to +9.6%]) or liver (P. vivax: +6.2% [CI -8.7% to +21.1%], P. falciparum: -1.4% [CI -4.6% to +1.8%]) following infection with either species. In participants with P. vivax, hemoglobin, hematocrit, and platelet count decreased from baseline at the time of postinoculation imaging. Decrements in hemoglobin and hematocrit were significantly greater in participants with P. vivax infection compared to P. falciparum. The main limitations of this study are the small sample size and the inability of this tracer to differentiate between host and parasite metabolic activity. PET/MRI indicated greater splenic tropism and metabolic activity in early P. vivax infection compared to P. falciparum, supporting the hypothesis of splenic accumulation of P. vivax very early in infection. The absence of uptake in the bone marrow and liver suggests that, at least in early infection, these tissues do not harbor a large parasite biomass or do not provoke a prominent metabolic response. PET/MRI is a safe and noninvasive method to evaluate infection-associated organ changes in morphology and glucose metabolism.

English

BACKGROUND The differentiation of tumour progression from treatment-induced changes is critical in evaluating response to therapy among patients with gliomas. Although conventional magnetic resonance imaging (MRI) is invaluable in the overall assessment of such lesions, it is often difficult to differentiate between these two entities. We wanted to evaluate the role of contrast-enhanced MRI (CE MRI) and magnetic resonance spectroscopy (MRS) and correlation with 99 m Tc Sestamibi single-photon emission tomography (SPECT) in differentiating tumour progression from post-therapy changes in patients with glioma. METHODS This was a cross-sectional study. Being a rare disease, all adult patients (25 in number) with brain glioma reporting to the hospital for over a period of 12 months were included in the study. CE MRI, MRS and SPECT were performed at three months, six months and 12 months’ post-surgery and radiotherapy. The ratios for choline (Cho) / N-acetyl aspartate (NAA) and choline (Cho) creatine (Cr) were obtained from the areas suspicious for tumour progression on CE MRI and were correlated with the presence or absence of uptake on SPECT. These findings were correlated with the patients’ clinical course and tumour histopathology. RESULTS Both choline (Cho) / N-acetyl aspartate (NAA) and choline (Cho) / creatine (Cr) ratios had high detection rates for tumour progression when cut-off values of &gt; 1.75 were used. For the Cho / NAA ratio, the sensitivity and specificity were 93.7 % and 100 %, respectively. The sensitivity and specificity for the Cho / Cr ratio were 81.3 % and 88.9 %, respectively. The sensitivity and specificity of 99 m Tc Sestamibi SPECT were 87.5 % and 100 %, respectively. CONCLUSIONS MRS and SPECT have high sensitivity and specificity for diagnosing tumour progression and must be used in conjunction with conventional CE MRI in the posttherapy setting. KEYWORDS Glioma, Progression, Post-Therapy Changes, MRI, MRS, SPECT