Diagnostic imaging of the diabetic foot: an EANM evidence-based guidance.

PURPOSE: Consensus on the choice of the most accurate imaging strategy in diabetic foot infective and non-infective complications is still lacking. This document provides evidence-based recommendations, aiming at defining which imaging modality should be preferred in different clinical settings. METHODS: This working group includes 8 nuclear medicine physicians appointed by the European Association of Nuclear Medicine (EANM), 3 radiologists and 3 clinicians (one diabetologist, one podiatrist and one infectious diseases specialist) selected for their expertise in diabetic foot. The latter members formulated some clinical questions that are not completely covered by current guidelines. These questions were converted into statements and addressed through a systematic analysis of available literature by using the PICO (Population/Problem-Intervention/Indicator-Comparator-Outcome) strategy. Each consensus statement was scored for level of evidence and for recommendation grade, according to the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria. RESULTS: Nine clinical questions were formulated by clinicians and used to provide 7 evidence-based recommendations: (1) A patient with a positive probe-to-bone test, positive plain X-rays and elevated ESR should be treated for presumptive osteomyelitis (OM). (2) Advanced imaging with MRI and WBC scintigraphy, or [18F]FDG PET/CT, should be considered when it is needed to better evaluate the location, extent or severity of the infection, in order to plan more tailored treatment. (3) In a patient with suspected OM, positive PTB test but negative plain X-rays, advanced imaging with MRI or WBC scintigraphy + SPECT/CT, or with [18F]FDG PET/CT, is needed to accurately assess the extent of the infection. (4) There are no evidence-based data to definitively prefer one imaging modality over the others for detecting OM or STI in fore- mid- and hind-foot. MRI is generally the first advanced imaging modality to be performed. In case of equivocal results, radiolabelled WBC imaging or [18F]FDG PET/CT should be used to detect OM or STI. (5) MRI is the method of choice for diagnosing or excluding Charcot neuro-osteoarthropathy; [18F]FDG PET/CT can be used as an alternative. (6) If assessing whether a patient with a Charcot foot has a superimposed infection, however, WBC scintigraphy may be more accurate than [18F]FDG PET/CT in differentiating OM from Charcot arthropathy. (7) Whenever possible, microbiological or histological assessment should be performed to confirm the diagnosis. (8) Consider appealing to an additional imaging modality in a patient with persisting clinical suspicion of infection, but negative imaging. CONCLUSION: These practical recommendations highlight, and should assist clinicians in understanding, the role of imaging in the diagnostic workup of diabetic foot complications.

Role of 18F-NaF PET/CT in bone metastases.

The use of 18F sodium fluoride (18F-NaF) in positron emission tomography (PET/CT) is increasing. This resurgence of an old tracer has been driven by several factors, including its superior diagnostic performance over standard 99mTc-based bone scintigraphy (BS), availability of PET/CT imaging systems, a shortened examination time and an increase in the number of regional commercial PET radiotracer distribution. In this special article, we aimed to highlight the current place of the 18F-NaF PET/CT in the imaging of bone metastases (BM) in a variety of malignancies. A special focus is given to the following ones: breast cancer (BC), prostate cancer (PCa). Also, other malignancies such as bladder cancer, lung cancer, thyroid cancer, multiple myeloma, head and neck cancer, hepatocellular carcinoma have been addressed. At last, we summarize the advantages and limits of the 18F-NaF PET/CT compared to other imaging modalities in these settings.

The role of positron computed tomography (PET/CT) in lung cancer staging.

Lung cancer is the leading cause of cancer-related mortalities with the rate of incidence reaching about 1.5 million cases per year worldwide. Approximately 350 people die each day from lung cancer in USA-nearly 2.5 times more than the number of people who die from colorectal cancer (CRC), which is the second leading cause of cancer death overall. In 2023, an estimated 238,340 people (117,550 men and 120,790 women) will be diagnosed with lung cancer, and 127,070 people will die from the disease. Although approximately 80% of lung cancers are caused by cigarette smoking, the toll among people who have never smoked is substantial, ranking among the top 10 causes of cancer death when categorized separately. Lung cancer encompasses a variety of biologically distinct tumours. The two primary types of lung cancer are non-small cell lung cancer (NSCLC), which accounts for 81% of cases, and small cell lung cancer (SCLC), which accounts for 14% of cases. NSCLC is further categorized as adenocarcinoma, which is slightly more common in women, followed by squamous cell carcinoma and large cell carcinoma.

Artificial intelligence in Nuclear Medicine Physics and Imaging.

No one can deny the significant impact of artificial intelligence (AI) on everyday life, especially in the health sector where it has emerged as a crucial and beneficial tool in Nuclear Medicine (NM) and molecular imaging. The objective of this review is to provide a summary of the various applications of AI in single-photon emission computed tomography (SPECT) and positron emission tomography (PET), with or without anatomical information (CT or magnetic resonance imaging (MRI)). This review analyzes subsets of AI, such as machine learning (ML) and Deep Learning (DL), and elaborates on their applications in NM imaging (NMI) physics, including the generation of attenuation maps, estimation of scattered events, depth of interaction (DOI), time of flight (TOF), NM image reconstruction (optimization of the reconstruction algorithm), and low dose imaging.

[18F]FDG PET/CT in rheumatoid arthritis.

[18F]fluorodeoxyglucose (FDG) PET/CT can be used to image the inflammation in rheumatoid arthritis. Specifically, the synovial metabolic activity can be evaluated visually and measured using standard uptake values. Fluorine-18-labeled Sodium fluoride (NaF) PET/CT can be used to determine synovial osteoblastic activity. Response assessment using FDG PET/CT is routine in many cancers and this is now an emerging technique for rheumatoid arthritis. Vasculitis in rheumatoid arthritis (RA) can be also studied with FDG PET/CT and aortic calcification with NaF PET/CT. These techniques could be useful in determining RA disease severity. FDG PET/CT is a useful technique to exclude underlying malignancy when RA does not follow the expected course. A number of novel tracers are being studied with regard to their applicability in rheumatoid arthritis and some of these could even be used in a theranostic manner in the future.

HER-2 breast cancer treatment induced mediastinal sarcoid like reaction depicted on 18F-FDG PET/CT.

This is a case of a woman with breast cancer, who developed mediastinal sarcoid-like reaction, depicted on PET/CT, which was histologically confirmed, following treatment with trastuzumab and pertuzumab. The development of noncaseating granulomas in patients who do not fulfill the criteria for systemic sarcoidosis is known as sarcoid-like reaction, having been described in association with trastuzumab in a few case reports, but none with pertuzumab. Physicians should be aware of the potentially higher rate of sarcoid-like reaction in patients receiving HER-2 treatment. The symmetric pattern of mediastinal lymphadenopathy, although indicative, is not pathognomonic for sarcoid-like reaction, and biopsy is necessary to exclude disease progression.

Nuclear Medicine and Oncology in the COVID-19 pandemic era.

The coronavirus disease 2019 (COVID-19) global pandemic poses a significant challenge to the national health systems. Not only China, the first country that experienced the health crisis since last December, but the rest of the world, is facing an unprecedented global health crisis, the most serious crisis in a century, with social and economic impact. However, the most important impact of the new pandemic is the human impact. Till 4th of June 2020, coronavirus SARS-CoV-2, causing COVID-19 disease, has infected more than 65000.000 people and has been responsible for more than 386000 deaths globally. The first priority of public health authorities is to contain and mitigate the spread and infection rate of the coronavirus SARS-CoV-2, distributing the number of infections over time and, if possible, reduce the incidence of the disease (COVID-19) it causes. A critical task for health systems confronted with the spread of the coronavirus is to protect the health of all citizens, so this requires that both diagnosis/testing and appropriate care should be readily available, affordable, and provided in a safe environment. The health care systems of many developed countries failed to demonstrate a satisfactory response to the increased demand for acute care hospital beds, ventilators, emergency services, diagnostics tests, support equipment for their COVID-19 patients, availability of essential medicines, protective equipment for their staff etc. Nuclear Medicine (NM) departments and their staff, in spite of the fact that not being in the front line of the pandemic response, have experienced a dramatic alteration in their daily clinical activity, trying to adapt their clinical routine to the new environment. There are several issued guidance from national and international organizations, trying to help to cope with suspected or verified COVID-19 patients. Patients with cancer are thought to be more susceptible and have higher morbidity and mortality rates from COVID-19 than the general population. In the current article, our aim is to present measures, guidance and thoughts that should be considered for the cancer patients.

Skeletal Metastases and Benign Mimics on NaF PET/CT: A Pictorial Review.

OBJECTIVE: The aim of this article is to present examples in which sodium fluoride labelled with 18F (NaF) bone PET/CT would be a useful adjunct to guide complex clinical decisions about the staging, restaging, and treatment approach for patients with skeletal metastases and benign causes of NaF activity that can be mistaken for bone metastases. We present a pictorial review of selected cases of this cohort of patients. CONCLUSION: NaF PET/CT hybrid fusion imaging is extremely useful in identifying potential causes of pain in patients with malignancies that have an affinity for skeletal metastases. This technique can help detect bone metastases, in problem solving, and to direct appropriate management.

Review of artificial intelligence clinical applications in Nuclear Medicine.

This paper provides an in-depth analysis of the clinical applications of artificial intelligence (AI) in Nuclear Medicine, focusing on three key areas: neurology, cardiology, and oncology. Beginning with neurology, specifically Alzheimer's disease and Parkinson's disease, the paper examines reviews on diagnosis and treatment planning. The same pattern is followed in cardiology studies. In the final section on oncology, the paper explores the various AI applications in multiple cancer types, including lung, head and neck, lymphoma, and pancreatic cancer.

Towards improved diagnosis: radiomics and quantitative biomarkers in 18F-PSMA-1007 and 18F-fluorocholine PET/CT for prostate cancer recurrence.

OBJECTIVE: This study compared the radiomic features and quantitative biomarkers of 18F-PSMA-1007 [prostate-specific membrane antigen (PSMA)] and 18F-fluorocholine (FCH) PET/computed tomography (CT) in prostate cancer patients with biochemical recurrence (BCR) enrolled in the phase 3, prospective, multicenter BIO-CT-001 trial. METHODS: A total of 106 patients with BCR, who had undergone primary definitive treatment for prostate cancer, were recruited to this prospective study. All patients underwent one PSMA and one FCH PET/CT examination in randomized order within 10 days. They were followed up for a minimum of 6 months. Pathology, prostate-specific antigen (PSA), PSA doubling time, PSA velocity, and previous or ongoing treatment were analyzed. Using LifeX software, standardized uptake value (SUV) maximum, SUVmean, PSMA and choline total volume (PSMA-TV/FCH-TV), and total lesion PSMA and choline (TL-PSMA/TL-FCH) of all identified metastatic lesions in both tracers were calculated. RESULTS: Of the 286 lesions identified, the majority 140 (49%) were lymph node metastases, 118 (41.2%) were bone metastases and 28 lesions (9.8%) were locoregional recurrences of prostate cancer. The median SUVmax value was significantly higher for 18F-PSMA compared with FCH for all 286 lesions (8.26 vs. 4.99, respectively, P < 0.001). There were statistically significant differences in median SUVmean, TL-PSMA/FCH, and PSMA/FCH-TV as per table 2 between the two radiotracers (4.29 vs. 2.92, 1.97 vs. 1.53, and 7.31 vs. 4.37, respectively, P < 0.001). The correlation between SUVmean/SUVmax and PSA level was moderate, both for 18F-PSMA (r = 0.44, P < 0.001; r = 0.44, P < 0.001) and FCH (r = 0.35, P < 0.001; r = 0.41, P < 0.001). TL-PSMA/FCH demonstrated statistically significant positive correlations with both PSA level and PSA velocity for both 18F-PSMA (r = 0.56, P < 0.001; r = 0.57, P < 0.001) and FCH (r = 0.49, P < 0.001; r = 0.51, P < 0.001). While patients who received hormone therapy showed higher median SUVmax values for both radiotracers compared with those who did not, the difference was statistically significant only for 18F-PSMA (P < 0.05). CONCLUSION: Our analysis using both radiomic features and quantitative biomarkers demonstrated the improved performance of 18F-PSMA-1007 compared with FCH in identifying metastatic lesions in prostate cancer patients with BCR.

Review of the role of MRI and 18 F-sodium fluoride PET/computed tomography in the characterisation of spinal bone metastases in a cohort of patients with breast cancer.

PURPOSE: The purpose of the study was to compare the diagnostic accuracy and relative usefulness of MRI and 18 F-NaF (sodium fluoride) PET/computed tomography (CT) for detection of spinal bone metastases in a cohort of patients with high-risk breast cancer (BrCa). METHODS: A retrospective study was conducted of patient and lesion-based analyses on 66 consecutive patients (median age, 62.5 years; age range, 33-91 years) who underwent Spinal MRI as well as 18 F-NaF PET-CT for restaging of newly diagnosed recurrent BrCa with no previous bone metastases. Both scans were performed within 20 days of each other. Review of prior images, clinical decisions, multi-disciplinary team discussions and decisions as well as follow-up information including scans and definitive tests was performed at least 12 months after the initial scans. RESULTS: Of the 66 patients reviewed, 26 patients had documented spinal bone metastases on one or both modalities, while 40 patients were considered bone disease free on both modalities and this was confirmed on follow-up. On lesion-based analysis, the findings of 18 F-NaF PET-CT and spinal MRI were concordant in 51 patients (77.3%). In the remaining patients, 18 F-NaF PET/CT detected more lesions in 4 patients (7.6%) and MRI detected more lesions in 10 patients (15.1%). Interestingly, there was a very high, 97 % concordance (64 patients) between spinal MRI and 18 F-NaF PET-CT when staging of spinal bone metastasis was taken into consideration. In one patient MRI identified two spinal bone metastases which were not seen on 18 F-NaF PET/CT; and, in one patient 18 F-NaF PET/CT showed few spinal bone metastases when no lesion was seen on MRI. CONCLUSIONS: Our study showed a high level of concordance between 18 F NaF PET-CT and spinal MRI within the setting of detection of bone lesions in the spine in a cohort of patients with high-risk BrCa. In our opinion, this high level of concordance negates the need to perform both tests although each test may be indicated for slightly different reasons. Further longitudinal studies across a longer duration and more centres may provide more definitive answers.

Update on Imaging of Inflammatory Arthritis and Related Disorders.

Arthritis and other rheumatic disorders are very frequent in the general population and responsible for a huge physical and disability burden to affected patients as well as a major cost to the society. Precise evaluation often relies on clinical data only but additional imaging may be required i) for a more objective assessment of the disease status, such as in rheumatoid arthritis (RA) or ankylosing spondyloarthritis (AS), ii) for providing prognostic information and evaluating response to treatment or iii) for establishing diagnosis, in patients with unclear clinical picture, such as polymyalgia rheumatica (PMR) and large-vessel vasculitis (LVV). Besides radiological techniques (x-rays, ultrasound, and MRI), functional and molecular imaging has emerged as a valid tool for this purpose in several disorders. Bone scanning has long been a method of choice but is now more used as a triage tool in patients with unclear complaints, including degenerative disorders (eg osteoarthritis). 18F-FDG-PET/CT (FDG) proved efficient in assessing the extent of the disease and response to treatment in RA and related disorders, and to provide accurate diagnosis in some systemic disorders, including PMR and LVV. Based on glucose metabolism, FDG-PET/CT is able to show increased metabolism in peripheral cells involved in inflammation (eg neutrophils, lymphocytes or monocytes/macrophages) but also in fibroblasts that proliferate in the pannus. The lack of specificity of FDG is a limitation and many alternative tracers were developed at the preclinical stage or applied in the clinics, especially within clinical trials. They include imaging of macrophages using translocator protein (TSPO), folate-receptors or other targets on activated cells. These new tools will undoubtedly become more and more available in the everyday clinical workup of patients with rheumatisms. Finally, it should be kept in mind that a very simple tracer, 18F-fluoride is widely more performant in AS than FDG.

Comparison of 18F-PSMA-1007 and 18F-Choline PET/CT in prostate cancer patients with biochemical recurrence: a phase 3, prospective, multicenter, randomized study.

OBJECTIVES: This prospective, multicenter, open-label, randomized, crossover trial study was to evaluate the diagnostic performance of 18F-PSMA-1007 (PSMA) vs. 18F-Choline PET/CT (FCH) in prostate cancer (PCa) patients (pts) with biochemical recurrence (BCR). METHODS: One hundred eighty-six pts, who have undergone primary definitive treatment for PCa with BCR, were recruited to this prospective study. All pts underwent one PSMA and one FCH PET/CT examination in randomized order within a time frame of 8 days and were followed up for at least 6 months (182 ±â€…10 days). RESULTS: Recurrence of PCa was observed in 176 out of 186 pts. The overall correct detection rate (DR) was 84% (95% CI 0.7967-0.8830) for PSMA and 69% (95% CI 0.6191-0.7489) for FCH, yielding a difference in proportion of 16% ( P  < 0.0001). PSMA had a sensitivity of 0.8464 and FCH 0.6857 with an odds ratio of 2.5259 ( P  < 0.0001), with statistically significant greater sensitivity of PSMA (ORs, 2.7877 and 2.1283 respectively) ( P  < 0.0001). PET/CT imaging led to a more accurate diagnosis in 166 (89.2%) pts, of which PSMA had contributed more than FCH in 91 (54.8%) of them. The DR for cutoff point PSA ≤ 1 ng/ml was higher for PSMA compared to FCH (61.8% vs. 39.5%). DR value of 51.6% for PSMA reached at PSA ≤ 0.3 ng/ml, while FCH reached that DR value with PSA ≤ 2.2 ng/ml. CONCLUSION: 18F-PSMA-1007 is more efficacious than 18F-Choline for the identification metastatic lesions both in patient and in regional level analysis in PCa patients with BCR.

Positron Emission Tomography/Computed Tomography Alert Finding in an Esophageal Cancer Patient.

Emergency pathologies often accompany malignancies. We herein report a case of pulmonary abscess in a patient with esophageal cancer which was depicted during the F-18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) staging study. The patient's history of recent dilatation of the cancer stenosis in adjunct to the previous CT lung imaging, which was normal, made evident the diagnosis of the pulmonary abscess due to the perforation of the esophageal neoplasm. This life-threatening condition was promptly referred and successfully managed.

FDG uptake in axillary lymph nodes after vaccination against pandemic (H1N1).

OBJECTIVE: To alert the imaging community to potential false positive findings related to current immunization programmes against H1N1 influenza virus. METHODS: We reviewed 10 patients referred for positron emission tomography/computed tomography (PET/CT) who had undergone recent vaccination. RESULTS: All studies showed( 18)F-fluorodeoxyglucose (FDG) uptake in the draining axillary lymph nodes close to the vaccination site, while low-dose CT revealed lymph nodes ranged between 0.5 cm and 1.2 cm at the same site. CONCLUSION: This potential pitfall in PET/CT should be borne in mind during current vaccination programmes.

False-Positive 18F-PSMA-1007 and True-Negative 18F-Fluorocholine PET/CT Splenic Hemangioma.

A 62-year-old man with prostate cancer underwent both F-PSMA-1007 and F-fluorocholine PET/CT studies for biochemical recurrence. F-PSMA-1007 PET/CT outperformed F-fluorocholine PET/CT in detecting lymph node metastases in the pelvis and retroperitoneum, whereas the former showed a focus of increased uptake in the spleen not seen on F-fluorocholine. The F-PSMA-1007 -avid lesion corresponded to a splenic hemangioma, which was initially detected in an MRI scan 10 years ago, unchanged in size. This case shows different features of F-PSMA-1007 and F-fluorocholine uptake, in an incidentally detected splenic hemangioma, alerting PET/CT reports for possible pitfall.

Rib Fractures Mimicking Bone Metastases in 18F-PSMA-1007 PET/CT for Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a membrane glycoprotein that is overexpressed in prostate cancer cells. It is also expressed in other normal tissues and several other malignant and benign diseases. We present a case of a 69-year-old man with history of prostate adenocarcinoma who underwent F-PSMA-1007 PET/CT due to suspected biochemical recurrence. PET/CT showed F-PSMA-1007 uptake in healing rib fractures with no other pathologic findings. Clinicians reporting F-PSMA-1007 PET/CT should be aware of this potential pitfall, especially in nontypical trauma pattern (eg, solitary osseous lesion) mimicking bone metastases.

Renal Manifestation of Birt-Hogg-Dubé Syndrome Depicted by 18F-fludeoxyglucose Positron Emission Tomography/Computed Tomography in a Patient with Hurtle Cell Thyroid Malignancy.

Birt-Hogg-Dubé (BHD) syndrome is an autosomal dominant genetic disorder characterized by small papular skin lesions (fibrofolliculomas) causing susceptibility to kidney cancer, renal and pulmonary cysts, spontaneous pneumothoraces, and several noncutaneous tumors. We report a case of a 67-year-old woman, with a previous history of right hemithyroidectomy for adenomatous lesion. She presented with a swelling in the right thyroid bed that on subsequent biopsy revealed features of metastatic carcinoma. 18F-fludeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) performed for the detection of primary malignancy showed increased high-grade metabolic activity in the right supraclavicular soft tissue mass extending into the superior mediastinum. Moreover, on low-dose CT, there have been bilateral renal interpolar cortical lesions with mild metabolic activity. Given the fact that the right neck mass was highly unlikely to represent renal metastases in the absence of widespread metastatic disease, surgical excision of the right neck mass was performed. The histology of the mass was in keeping with hurtle cell thyroid carcinoma. In regard to renal lesions, bilateral partial nephrectomy was performed, which was consistent with chromophobe renal cell carcinoma, raising the suspicion of BHD that was confirmed by the subsequent genetic evaluation. It is well established that 18F-FDG PET/CT study is not an optimal modality for evaluation of renal lesions. However, careful assessment of the CT features in conjunction with the associated metabolic activity of the 18F-FDG PET component increases the diagnostic accuracy of PET/CT.