A Rare False-Positive Whole-Body Scan in a Patient With Differentiated Thyroid Cancer: Unilateral Conjunctival Concretions.

ABSTRACT: 131 I has been used effectively over the years in both diagnosis and therapy of differentiated thyroid cancer (DTC). Although whole-body scan with 131 I is a highly sensitive tool for detecting normal thyroid tissue and metastasis of DTC, it is not specific; therefore, false-positive images can be seen in clinical practice, and their recognition is critical for correct management. Evaluation of false-positive uptake is important because it may be confused with metastatic involvement. Here, we present a rare false-positive result of whole-body scan in a patient with DTC. To our knowledge, it is the first report on 131 I uptake of conjunctival concretions.

Gastrointestinal radionuclide imaging in pediatric age group.

Pediatric gastrointestinal imaging plays a crucial role in evaluating and managing digestive system disorders in children. This comprehensive review dives into the nuances of pediatric gastrointestinal imaging techniques, focusing on three specific modalities: gastric emptying scintigraphy (GES), intestinal transit scintigraphy (ITS), and gastrointestinal bleeding scintigraphy. GES involves real-time monitoring of stomach emptying using radiotracers and gamma camera technology. While challenges exist in standardizing protocols due to age-specific meal compositions, GES remains pivotal in diagnosing motility disorders, gastroesophageal reflux, and abdominal pain in children. ITS, utilizing [67Ga], provides insights into gastrointestinal motility disorders such as Hirschsprung disease. It aids in whole-gut transit evaluation, guiding surgical interventions and improving long-term clinical outcomes. Gastrointestinal bleeding scintigraphy, employing [99mTc], assists in diagnosing conditions like Meckel's diverticulum and occult bleeding, offering continuous monitoring to pinpoint the bleeding site along the entire gastrointestinal tract. SPECT-CT improves the accuracy and the standards of care. Each technique's protocol details, clinical indications, and diagnostic capabilities are thoroughly discussed, highlighting the importance of these non-invasive, functional imaging modalities in pediatric gastroenterology.

Unsupervised OCT image despeckling with ground-truth- and repeated-scanning-free features.

Optical coherence tomography (OCT) can resolve biological three-dimensional tissue structures, but it is inevitably plagued by speckle noise that degrades image quality and obscures biological structure. Recently unsupervised deep learning methods are becoming more popular in OCT despeckling but they still have to use unpaired noisy-clean images or paired noisy-noisy images. To address the above problem, we propose what we believe to be a novel unsupervised deep learning method for OCT despeckling, termed Double-free Net, which eliminates the need for ground truth data and repeated scanning by sub-sampling noisy images and synthesizing noisier images. In comparison to existing unsupervised methods, Double-free Net obtains superior denoising performance when trained on datasets comprising retinal and human tissue images without clean images. The efficacy of Double-free Net in denoising holds significant promise for diagnostic applications in retinal pathologies and enhances the accuracy of retinal layer segmentation. Results demonstrate that Double-free Net outperforms state-of-the-art methods and exhibits strong convenience and adaptability across different OCT images.

Incidental 68Ga-DOTATATE uptake in thyroid nodules: Is guideline-directed management still appropriate?

BACKGROUND: Fluorodeoxyglucose uptake on positron emission tomography imaging has been shown to be an independent risk factor for malignancy in thyroid nodules. More recently, a new positron emission tomography radiotracer-Gallium-68 DOTATATE-has gained popularity as a sensitive method to detect neuroendocrine tumors. With greater availability of this imaging, incidental Gallium-68 DOTATATE uptake in the thyroid gland has increased. It is unclear whether current guideline-directed management of thyroid nodules remains appropriate in those that are Gallium-68 DOTATATE avid. METHODS: We retrospectively reviewed Gallium-68 DOTATATE positron emission tomography scans performed at our institution from 2012 to 2022. Patients with incidental focal Gallium-68 DOTATATE uptake in the thyroid gland were included. Fine needle aspiration biopsies were characterized via the Bethesda System for Reporting Thyroid Cytopathology. Bethesda III/IV nodules underwent molecular testing (ThyroSeq v3), and malignancy risk ≥50% was considered positive. RESULTS: In total, 1,176 Gallium-68 DOTATATE PET scans were reviewed across 837 unique patients. Fifty-three (6.3%) patients demonstrated focal Gallium-68 DOTATATE thyroid uptake. Nine patients were imaged for known medullary thyroid cancer. Forty-four patients had incidental radiotracer uptake in the thyroid and were included in our study. Patients included in the study were predominantly female sex (75%), with an average age of 62.9 ± 13.9 years and a maximum standardized uptake value in the thyroid of 7.3 ± 5.3. Frequent indications for imaging included neuroendocrine tumors of the small bowel (n = 17), lung (n = 8), and pancreas (n = 7). Thirty-three patients underwent subsequent thyroid ultrasound. Sonographic findings warranted biopsy in 24 patients, of which 3 were lost to follow-up. Cytopathology and molecular testing results are as follows: 12 Bethesda II (57.1%), 6 Bethesda III/ThyroSeq-negative (28.6%), 1 Bethesda III/ThyroSeq-positive (4.8%), 2 Bethesda V/VI (9.5%). Four nodules were resected, revealing 2 papillary thyroid cancers, 1 neoplasm with papillary-like nuclear features, and 1 follicular adenoma. There was no difference in maximum standardized uptake value between benign and malignant nodules (7.0 ± 4.6 vs 13.1 ± 5.7, P = .106). Overall, the malignancy rate among patients with sonography and appropriate follow-up was 6.7% (2/30). Among patients with cyto- or histopathology, the malignancy rate was 9.5% (2/21). There were no incidental cases of medullary thyroid cancer. CONCLUSION: The malignancy rate among thyroid nodules with incidental Gallium-68 DOTATATE uptake is comparable to rates reported among thyroid nodules in the general population. Guideline-directed management of thyroid nodules remains appropriate in those with incidental Gallium-68 DOTATATE uptake.

A Rare Case of Abnormal Diffuse Brain Uptake on an 123I MIBG Scan in a Patient With High-Risk Neuroblastoma.

ABSTRACT: 123I-meta-iodobenzylguanidine (123I-MIBG) is extensively used for initial staging and response evaluation in children with neuroblastoma. Physiological uptake of 123I-MIBG occurs in the salivary glands, liver, adrenal gland, myocardium, bowel, and thyroid gland. 123I-MIBG cannot cross an intact blood-brain barrier. We present the rare case of a 3-year-old boy with neuroblastoma and meningeal metastases who underwent an 123I-MIBG scan for disease restaging that showed abnormal brain uptake. Abnormal MIBG uptake in the brain can occur if there is disruption of the blood-brain barrier either secondary to metastases or after damage to blood-brain barrier.

Concordancia entre SPECT portátil y la gammagrafía convencional para detección de ganglio centinela en cáncer de mama / Concordance between freehand SPECT and conventional scintigraphy for sentinel lymph node detection in breast cancer

Introducción: La SPECT portátil puede ser una técnica de imagen útil para la planificación preoperatoria de la biopsia selectiva del ganglio centinela (BSGC) ya que permite la localización del ganglio centinela (GC) mediante imágenes tomográficas en 3D y en tiempo real y determina su profundidad, después de unos minutos de exploración. El objetivo del estudio fue evaluar la correlación entre el número de GC detectados entre las imágenes de la SPECT portátil y la linfogammagrafía (LG). Materiales y métodos: Cien pacientes con diagnóstico de cáncer de mama infiltrante y sin evidencia clínica de afectación ganglionar, se sometieron prospectivamente a una BSGC. El estudio preoperatorio incluyó imágenes de SPECT portátil a los 15 min tras la inyección y de LG a los 25 y 60-90 min (precoz y tardía). Se analizó el acuerdo observado y se realizó un estudio de concordancia entre el número de GC detectados con SPECT portátil y LG. Resultados: El acuerdo observado en la detección de GC entre SPECT portátil y LG precoz fue del 72%; entre SPECT portátil y LG tardía del 85%, y entre la LG precoz y la tardía de un 87%. En el estudio de concordancia se registró una concordancia moderada entre la SPECT portátil y la LG precoz (coeficiente kappa: 0,42); una concordancia moderada-alta entre la SPECT portátil y la LG tardía (coeficiente kappa: 0,60), y una concordancia de moderada-alta entre la LG precoz y la tardía (coeficiente kappa: 0,70), sin diferencias significativas entre ellos (valor p=0,16). Conclusión: La SPECT portátil presentó una concordancia moderada-alta con los estudios de imagen convencional y podría ser una alternativa válida para el estudio prequirúrgico de la BSGC en el cáncer de mama.(AU)

Introduction: Freehand SPECT can be a useful imaging technique for preoperative planning of sentinel lymph node biopsy (SLNB) as it allows localization of the sentinel node by 3D and real-time tomographic imaging and determines its depth after a few minutes of scanning. The aim of the study was to evaluate the correlation between the number of detected SNs between freehand SPECT images and lymphoscintigraphy (LS). Materials and methods: One hundred patients with a diagnosis of invasive breast cancer and no clinical evidence of lymph node involvement prospectively underwent SLNB. The preoperative study included freehand SPECT imaging at 15min after injection and LS imaging at 25 and 60–90min after injection (early and late). The observed agreement was analyzed and a concordance study was performed between the number of SNs detected with freehand SPECT and LS. Results: The observed agreement in the detection of SNs between freehand SPECT and early LS was 72%; between freehand SPECT and late LS was 85%; and between early and late LS was 87%. In the concordance study, there was moderate concordance between freehand SPECT and early LS (kappa coefficient: 0.42); moderate-high concordance between freehand SPECT and late LS (kappa coefficient: 0.60); and moderate-high concordance between early and late LS (kappa coefficient: 0.70), with no significant differences between them (p-value=0.16). Conclusion: Freehand SPECT showed a moderate-high concordance with conventional imaging studies and could be a valid alternative for the presurgical study of SLNB in breast cancer.(AU)

Nuclear medicine and pediatric nephro-urology: a long-lasting successful partnership.

Congenital anomalies of the kidney and urinary tract, as well as urinary infections, are very frequent in children. After the clinical and laboratory evaluation, the first imaging procedure to be done is a renal and bladder ultrasound, but afterwards, a main contribution comes from nuclear medicine. Through minimally invasive and sedation-free procedures, nuclear medicine allows the evaluation of the functional anatomy of the urinary tract, and the quantification of renal function and drainage. If pediatric dosage cards provided by scientific societies are used, radiation exposure can also be low. In the pediatric conditions previously mentioned, nuclear medicine is used both for initial diagnosis and follow-up, mostly in cases of suspicion of ureteropelvic or ureterovesical junction syndromes, as well as vesicoureteral reflux or renal scars of febrile infectious episodes. Pediatric nephro-urology constitutes a significant workload of pediatric nuclear medicine departments. The following paragraphs are a revision of the renal radiopharmaceuticals, as well as the nuclear nephro-urology procedures - dynamic and static renal scintigraphy, and direct and indirect radionuclide cystography. A summary of the techniques, main indications, interpretation criteria and pitfalls will be provided. Some future directions for the field are also pointed out, among which the most relevant is the need for nuclear medicine professionals to use standardized protocols and integrate multidisciplinary teams with other pediatric and adult health professionals that manage these life-long pediatric pathologies, which are recognized as an important cause of adult chronic kidney disease.

Diagnosis and prognosis of abnormal cardiac scintigraphy uptake suggestive of cardiac amyloidosis using artificial intelligence: a retrospective, international, multicentre, cross-tracer development and validation study.

BACKGROUND: The diagnosis of cardiac amyloidosis can be established non-invasively by scintigraphy using bone-avid tracers, but visual assessment is subjective and can lead to misdiagnosis. We aimed to develop and validate an artificial intelligence (AI) system for standardised and reliable screening of cardiac amyloidosis-suggestive uptake and assess its prognostic value, using a multinational database of 99mTc-scintigraphy data across multiple tracers and scanners. METHODS: In this retrospective, international, multicentre, cross-tracer development and validation study, 16 241 patients with 19 401 scans were included from nine centres: one hospital in Austria (consecutive recruitment Jan 4, 2010, to Aug 19, 2020), five hospital sites in London, UK (consecutive recruitment Oct 1, 2014, to Sept 29, 2022), two centres in China (selected scans from Jan 1, 2021, to Oct 31, 2022), and one centre in Italy (selected scans from Jan 1, 2011, to May 23, 2023). The dataset included all patients referred to whole-body 99mTc-scintigraphy with an anterior view and all 99mTc-labelled tracers currently used to identify cardiac amyloidosis-suggestive uptake. Exclusion criteria were image acquisition at less than 2 h (99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid, 99mTc-hydroxymethylene diphosphonate, and 99mTc-methylene diphosphonate) or less than 1 h (99mTc-pyrophosphate) after tracer injection and if patients' imaging and clinical data could not be linked. Ground truth annotation was derived from centralised core-lab consensus reading of at least three independent experts (CN, TT-W, and JN). An AI system for detection of cardiac amyloidosis-associated high-grade cardiac tracer uptake was developed using data from one centre (Austria) and independently validated in the remaining centres. A multicase, multireader study and a medical algorithmic audit were conducted to assess clinician performance compared with AI and to evaluate and correct failure modes. The system's prognostic value in predicting mortality was tested in the consecutively recruited cohorts using cox proportional hazards models for each cohort individually and for the combined cohorts. FINDINGS: The prevalence of cases positive for cardiac amyloidosis-suggestive uptake was 142 (2%) of 9176 patients in the Austrian, 125 (2%) of 6763 patients in the UK, 63 (62%) of 102 patients in the Chinese, and 103 (52%) of 200 patients in the Italian cohorts. In the Austrian cohort, cross-validation performance showed an area under the curve (AUC) of 1·000 (95% CI 1·000-1·000). Independent validation yielded AUCs of 0·997 (0·993-0·999) for the UK, 0·925 (0·871-0·971) for the Chinese, and 1·000 (0·999-1·000) for the Italian cohorts. In the multicase multireader study, five physicians disagreed in 22 (11%) of 200 cases (Fleiss' kappa 0·89), with a mean AUC of 0·946 (95% CI 0·924-0·967), which was inferior to AI (AUC 0·997 [0·991-1·000], p=0·0040). The medical algorithmic audit demonstrated the system's robustness across demographic factors, tracers, scanners, and centres. The AI's predictions were independently prognostic for overall mortality (adjusted hazard ratio 1·44 [95% CI 1·19-1·74], p<0·0001). INTERPRETATION: AI-based screening of cardiac amyloidosis-suggestive uptake in patients undergoing scintigraphy was reliable, eliminated inter-rater variability, and portended prognostic value, with potential implications for identification, referral, and management pathways. FUNDING: Pfizer.

Increasing Catecholamine Secretion Through NPY in Pheochromocytomas With False-Negative 123 I-MIBG Scintigraphy.

INTRODUCTION: 123 I-MIBG has been well established as a functional imaging tool, and 131 I-MIBG therapy is being considered for catecholamine-secreting tumors. Tumors with the characteristics of a noradrenergic biochemical phenotype, small, malignant, metastatic, extra-adrenal, bilateral, and hereditary, especially SDHx -related tumors, are reported to correlate with reduced MIBG uptake. However, the potential molecular mechanisms influencing MIBG uptake have been poorly studied. PATIENTS AND METHODS: To identify critical genes that may enhance MIBG accumulation in pheochromocytomas (PCCs), we performed RNA-seq analyses for 16 operated patients with PCCs (6 MIBG-negative and 10 MIBG-positive) combined with RT-qPCR for 27 PCCs (5 MIBG-negative and 22 MIBG-positive) and examined primary cultures of the surgical tissues. RESULTS: In the present study, 6 adrenal nodules of 66 nodules surgically removed from 63 patients with PCCs (9%) were MIBG negative. MIBG, a guanethidine analog of norepinephrine, can enter chromaffin cells through active uptake via the cellular membrane, be deposited in chromaffin granules, and be released via Ca 2+ -triggered exocytosis from adrenal chromaffin cells. When we compared expression of several catecholamine biosynthesis and secretion-associated genes between MIBG-negative and MIBG-positive tumors using transcriptome analyses, we found that neuropeptide Y, which is contained in chromaffin granules, was significantly increased in MIBG-negative tumors. NPY stimulated norepinephrine secretion dose-dependently in primary cell culture derived from MIBG-positive PCC. In our study, MIBG-negative PCCs were all norepinephrine-hypersecreting tumors. CONCLUSIONS: These data indicate that NPY upregulation in PCCs may stimulate chromaffin granule catecholamine secretion, which is associated with false-negative 123 I-MIBG scintigraphy.

Gastric Emptying Studies in Pediatrics: A Cincinnati Children's Hospital Experience.

Gastric emptying studies are routinely performed in many nuclear medicine departments; however, there are many different techniques used to perform the procedure across the country. Creating consistency in clinical practice will aid gastroenterologists in diagnosing and treating illnesses associated with abnormalities related to gastric emptying. In 2017, Cincinnati Children's Hospital adopted adult standards for pediatric gastric emptying studies that included a standard meal along with imaging over the course of 4 h. Gastric emptying studies are the second-highest-volume examination performed in the nuclear medicine section at Cincinnati Children's Hospital. Accommodating this volume required changes in the scheduling template, scheduling questionnaire, and epic order sets, as well as identification of specific days and locations for gastric emptying studies. Both protocol standardization and workflow optimization are critically important in creating consistency in patient care. Gastric emptying can be evaluated with solid food, liquid food, or solid and liquid food simultaneously. The methodology of the study is initially determined by the ordering provider but may require special accommodations based on what the patient will tolerate. In coordination with the ordering and interpreting physicians, the nuclear medicine technologists at Cincinnati Children's Hospital have the decision-making ability to deviate from the provider's request as necessary, which helps expedite workflow and eliminates wasted time. Any deviation from the standardized protocol is documented by the nuclear medicine technologist and incorporated into the final report by the interpreting physician, as dietary information is meaningful to the ordering provider. Reference values associated with the standardized or modified protocol are also included in the final report.

Change in Management After Radionuclide Gastric Emptying Studies Showing Slow Emptying.

The radionuclide gastric emptying study is the gold standard for the diagnosis of gastroparesis. Methods: We performed a retrospective analysis of 510 patients to evaluate how often a diagnosis of slow gastric emptying determined by gastric emptying scintigraphy (GES) changes clinical management at our institution. Results: We found evidence of gastroparesis in 100 patients. A change in management was recommended for 62% within 1 mo of the GES. Conclusion: Our results illustrate the importance of performing GES on patients with clinically suspected gastroparesis.

An Evaluation of Gastric Emptying Scintigraphy Protocols in Health Care Institutions When Compared with the Society of Nuclear Medicine and Molecular Imaging Procedure Guidelines.

This study aimed to analyze the compliance of health care institutions with the Society of Nuclear Medicine and Molecular Imaging (SNMMI) procedure guidelines for gastric emptying scintigraphy (GES). Methods: A 19-question survey on demographics and the GES protocol was conducted using a Google form. The demographic questions covered position, number of technologists in the department, location, type of health care institution, and number of GES studies per month. The protocol questions included patient preparation, meal preparation, withholding of scheduled medications, radiopharmaceutical type, and radiopharmaceutical dose. The survey was sent to 7 nuclear medicine Facebook groups and a list of clinical affiliates provided by the Indiana University School of Medicine Nuclear Medicine Program. Descriptive statistics were compiled for most questions. A Fisher exact test with a significance level of 0.05 was used to compare the type of health care institution with compliance with the SNMMI GES protocol regarding radiolabeling time, meal preparation, and meal components, as well as to compare the type of health care institution with the number of GES studies performed per institution. Results: In total, 240 people responded to the survey. Most were nonsupervisory nuclear medicine technologists (72%) in nonacademic institutions (72%) and groups with 4 or more technologists (62%). Of the respondents, 72% followed the SNMMI guideline of adding the radiopharmaceutical before cooking, but only 37% followed the meal component guideline. There was no significant association between the type of institution or the number of GES studies and compliance with radiolabeling time or with meal preparation or components. Most respondents asked patients to withhold medications per SNMMI guidelines and used the recommended radiopharmaceutical (99mTc-sulfur colloid, 95%) at the recommended dose (18.5-37 MBq, 84%). Conclusion: Although most respondents followed most aspects of the SNMMI guidelines for GES, more than half did not use the recommended meal of liquid egg whites. Compliance did not vary between academic and nonacademic institutions or between groups performing a large or a small number of GES studies.

Opportunistic screening with multiphase contrast-enhanced dual-layer spectral CT for osteoblastic lesions in prostate cancer compared with bone scintigraphy.

Our study aimed to compare bone scintigraphy and dual-layer detector spectral CT (DLCT) with multiphase contrast enhancement for the diagnosis of osteoblastic bone lesions in patients with prostate cancer. The patients with prostate cancer and osteoblastic bone lesions detected on DLCT were divided into positive bone scintigraphy group (pBS) and negative bone scintigraphy group (nBS) based on bone scintigraphy. A total of 106 patients (57 nBS and 49 pBS) was included. The parameters of each lesion were measured from DLCT including Hounsfield unit (HU), 40-140 keV monochromatic HU, effective nuclear numbers (Zeff), and Iodine no water (InW) value in non-contrast phase (N), the arterial phase (A), and venous phase (V). The slope of the spectral curve at 40 and 100 keV, the different values of the parameters between A and N phase (A-N), V and N phase (V-N), and hybrid prediction model with multiparameters were used to differentiate pBS from nBS. Receiver operating characteristic analysis was performed to compare the area under the curve (AUC) for differentiating the pBS group from the nBS group. The value of conventional HU values, slope, and InW in A-N and V-N, and hybrid model were significantly higher in the pBS group than in the nBS group. The hybrid model of all significant parameters had the highest AUC of 0.988, with 95.5% sensitivity and 94.6% specificity. DLCT with arterial contrast enhancement phase has the potential to serve as an opportunistic screening tool for detecting positive osteoblastic bone lesions, corresponding to those identified in bone scintigraphy.

Detection of CD40 Protein-Umbelliferone Interaction via Differential Scanning Fluorescence.

The investigation of interactions between different molecules is a crucial aspect of understanding disease pathogenesis and screening for drug targets. Umbelliferone, an active ingredient in Tibetan medicine Vicatia thibetica, exhibits an immunomodulatory effect with an unknown mechanism. The CD40 protein is a key target in the immune response. Therefore, this study employs the principle of differential scanning fluorescence technology to analyze the interactions between CD40 protein and umbelliferone using fluorescent enzyme markers. Initially, the stability of the protein fluorescent orange dye was experimentally verified, and the optimal dilution ratio of 1:500 was determined. Subsequently, it was observed that the temperature melting (Tm) value of CD40 protein tended to decrease with an increase in concentration. Interestingly, the interaction between CD40 protein and umbelliferone was found to enhance the thermal stability of CD40 protein. This study represents the first attempt to detect the binding potential of small molecule compounds and proteins using fluorescence microplates and fluorescent dyes. The technique is characterized by high sensitivity and accuracy, promising advancements in the fields of protein stability, protein structure, and protein-ligand interactions, thus facilitating further research and exploration.

COVID-19 Infection Percentage Estimation from Computed Tomography Scans: Results and Insights from the International Per-COVID-19 Challenge.

COVID-19 analysis from medical imaging is an important task that has been intensively studied in the last years due to the spread of the COVID-19 pandemic. In fact, medical imaging has often been used as a complementary or main tool to recognize the infected persons. On the other hand, medical imaging has the ability to provide more details about COVID-19 infection, including its severity and spread, which makes it possible to evaluate the infection and follow-up the patient's state. CT scans are the most informative tool for COVID-19 infection, where the evaluation of COVID-19 infection is usually performed through infection segmentation. However, segmentation is a tedious task that requires much effort and time from expert radiologists. To deal with this limitation, an efficient framework for estimating COVID-19 infection as a regression task is proposed. The goal of the Per-COVID-19 challenge is to test the efficiency of modern deep learning methods on COVID-19 infection percentage estimation (CIPE) from CT scans. Participants had to develop an efficient deep learning approach that can learn from noisy data. In addition, participants had to cope with many challenges, including those related to COVID-19 infection complexity and crossdataset scenarios. This paper provides an overview of the COVID-19 infection percentage estimation challenge (Per-COVID-19) held at MIA-COVID-2022. Details of the competition data, challenges, and evaluation metrics are presented. The best performing approaches and their results are described and discussed.