Ignasi Carrió’s research while affiliated with Autonomous University of Barcelona and other places

Purpose To improve reproducibility and predictive performance of PET radiomic features in multicentric studies by cycle-consistent generative adversarial network (GAN) harmonization approaches. Methods GAN-harmonization was developed to harmonize whole-body PET scans to perform image style and texture translation between different centers and scanners. GAN-harmonization was evaluated by application to two retrospectively collected open datasets and different tasks. First, GAN-harmonization was performed on a dual-center lung cancer cohort (127 female, 138 male) where the reproducibility of radiomic features in healthy liver tissue was evaluated. Second, GAN-harmonization was applied to a head and neck cancer cohort (43 female, 154 male) acquired from three centers. Here, the clinical impact of GAN-harmonization was analyzed by predicting the development of distant metastases using a logistic regression model incorporating first-order statistics and texture features from baseline ¹⁸ F-FDG PET before and after harmonization. Results Image quality remained high (structural similarity: left kidney $\ge$ ≥ 0.800, right kidney $\ge$ ≥ 0.806, liver $\ge$ ≥ 0.780, lung $\ge$ ≥ 0.838, spleen $\ge$ ≥ 0.793, whole-body $\ge$ ≥ 0.832) after image harmonization across all utilized datasets. Using GAN-harmonization, inter-site reproducibility of radiomic features in healthy liver tissue increased at least by $\ge$ ≥ 5 ± 14% (first-order), $\ge$ ≥ 16 ± 7% (GLCM), $\ge$ ≥ 19 ± 5% (GLRLM), $\ge$ ≥ 16 ± 8% (GLSZM), $\ge$ ≥ 17 ± 6% (GLDM), and $\ge$ ≥ 23 ± 14% (NGTDM). In the head and neck cancer cohort, the outcome prediction improved from AUC 0.68 (95% CI 0.66–0.71) to AUC 0.73 (0.71–0.75) by application of GAN-harmonization. Conclusions GANs are capable of performing image harmonization and increase reproducibility and predictive performance of radiomic features derived from different centers and scanners.

Presynaptic dopaminergic positron emission tomography (PET) imaging serves as an essential tool in diagnosing and differentiating patients with suspected parkinsonism, including idiopathic Parkinson’s disease (PD) and other neurodegenerative and non-neurodegenerative diseases. The PET tracers most commonly used at the present time mainly target dopamine transporters (DAT), aromatic amino acid decarboxylase (AADC), and vesicular monoamine type 2 (VMAT2). However, established standards for the imaging procedure and interpretation of presynaptic dopaminergic PET imaging are still lacking. The goal of this international consensus is to help nuclear medicine practitioners procedurally perform presynaptic dopaminergic PET imaging. A multidisciplinary task group formed by experts from various countries discussed and approved the consensus for presynaptic dopaminergic PET imaging in parkinsonism, focusing on standardized recommendations, procedures, interpretation, and reporting. This international consensus and practice guideline will help to promote the standardized use of presynaptic dopaminergic PET imaging in parkinsonism. It will become an international standard for this purpose in clinical practice.

Aim We performed a systematic survey to assess the existing gaps in Europe in multidisciplinary education for integration of radioligand therapy (RLT) into cancer care and to obtain detailed information on the current limitations and key contents relevant. Methods A high-quality questionnaire, with emphasis on survey scales, formulation, and validity of the different items, was designed. An expert validation process was undertaken. The survey was circulated among medical specialties involved in cancer treatment, universities, and nursing organizations. Questionnaires (156) were distributed, and 95 responses received. Results Sevety-eight percent of medical societies indicated that training in RLT was very important and 12% important. Eighty-eight percent indicated that their specialty training program included RLT. Twenty-six percent were satisfied with the existing structure of training in RLTs. Ninety-four percent indicated that the existing training is based on theory and hands-on experience. Main identified limitations were lack of centers ready to train and of personnel available for teaching. Sixty-five percent indicated that national programs could be expanded. Fifty percent of consulted universities indicated partial or scarce presence of RLT contents in their teaching programs. In 26% of the cases, the students do not have the chance to visit a RLT facility. A large majority of the universities are interested in further expansion of RLT contents in their curriculums. Nursing organizations almost never (44.4%) or occasionally (33.3%) include RLT contents in the education of nurses and technologists. Hands-on experience is almost never (38%) and sometimes (38%) offered. However, 67% of centers indicated high interest in expanding RLT contents. Conclusion Centers involved recognize the importance of the training and indicate a need for inclusion of additional clinical content, imaging analysis, and interpretation as well as extended hands-on training. A concerted effort to adapt current programs and a shift towards multidisciplinary training programs is necessary for proper education in RLT in Europe.

Radiotherapy or chemotherapy and new drugs and strategies in oncology can produce damage in normal organs and tissues affecting the quality of life of the patient. Pulmonary toxicity is frequently seen in patients treated with bleomycin or other chemotherapeutic agents. The most common clinical form of bleomycin pulmonary toxicity is the subacute condition, which may progress to lung fibrosis and death, if not recognized and appropriately managed. The diagnosis is usually established by a combination of clinical, radiographic, and pulmonary function test abnormalities. X-ray and high-resolution CT scan findings are used to identify pulmonary fibrosis. 67Ga-citrate scintigraphy has been used to detect and assess the extent of pulmonary toxicity related to bleomycin in patients who otherwise have normal chest radiographs. Since conventional CT scanning is not able to distinguish fibrosis from active inflammation, [18F]FDG-PET/CT has been suggested as a tool to indicate the resolution of disease activity. Moreover, [18F]FDG-PET/CT could be useful to detect early preclinical pneumonitis induced by bleomycin. Similarly, as pulmonary permeability can be altered by chemotherapy, 99mTc-DTPA aerosols can be used to assess a potential reduction of epithelial permeability. Acute radiation lung injury can occur within 1–3 months after radiation therapy of the thorax, whereas lung fibrosis can develop 6–24 months later, leading to progressive impairment of pulmonary function. Clinical manifestations, chest radiographs, and pulmonary function tests may help to establish an early diagnosis. 67Ga-citrate scintigraphic abnormalities can be demonstrated in the acute phase often before radiologic changes become apparent. Moreover, 111In-pentetreotide may have a role in the differential diagnosis of patients with complaints after radiotherapy and for monitoring response to corticosteroid therapy. [18F]FDG uptake in the irradiated region can be observed up to about 2 months following therapy. The persistence of activity beyond 8 weeks raises the likelihood of persistence of disease within the irradiated region. Lung scintigraphy with 99mTc-DTPA aerosol and 99mTc-MAA (macroaggregates of albumin) has been performed to assess radiation-induced ventilation/perfusion changes. Drugs for the treatment of abdominal malignancies, such as cisplatin and ifosfamide, and abdominal radiation can cause renal damage. Chemotherapy-induced nephropathy can be identified with quantitative measurement of glomerular filtration rate. 99mTc-DTPA has become the preferred radiopharmaceutical because of wide availability and low cost. 99mTc-DMSA scintigraphy can be used to establish tubular dysfunction induced by nephrotoxic drugs. Nuclear medicine techniques also offer the possibility to follow the clinical evolution of radiation nephropathy. In this scenario, 99mTc-MDP bone scintigraphy can show increased kidney uptake early after radiation when the treatment field has included the kidneys. Over the subsequent 6–12 months, the uptake decreases to normal or below normal levels, associated with the loss of function. Renography with 99mTc-DTPA can be performed to assess radiation nephropathy. The 99mTc-DTPA captopril renography test has been used to investigate the relation between small-vessel injury due to radiation and hypertension. Nuclear medicine examinations can play a role in the detection of radiation-induced digestive tract damage. In cancers of the cervix, endometrium, ovary, prostate, bladder, or rectum, radiation therapy is often required. Radiation proctitis is usually self-limited and resolves within a month after the conclusion of therapy. Damage of the small bowel is seen in 0.5–15% of the patients. Chronic injuries to the small bowel are manifest 6 and 24 months after radiation. Ileal dysfunction is due to bile acid malabsorption, to bacterial overgrowth in the small bowel, or to the combination of both. 75Se-homocholic acid conjugated with taurine (75Se-HCAT) and the [14C]glycocholic breath test can be used to differentiate between normal functioning ileum (both tests negative) and ileal dysfunction (one or both tests positive). The combination of both tests may allow the differentiation between bile acid malabsorption (75Se-HCAT positive) and bacterial overgrowth (75Se-HCAT negative). Radionuclide-based techniques may also help to document the benefit of innovative therapeutic approaches such as the use of somatostatin analogs (SOM230). In cases of radiotherapy- and chemotherapy-associated liver injury, radionuclide studies can be performed using 99mTc-iminodiacetic acid or 99mTc-colloid. In patients receiving radiotherapy, the most common finding is the loss of function of the part of the liver involved in the radiation field, with a reduced uptake in irradiated areas. Recently, acute radiation-induced hepatitis has been reported as a potential cause of false-positive findings of malignancy on [18F]FDG-PET scans. Moreover, radiotherapy esophagitis can be observed on [18F]FDG-PET scans. Leucocytes labeled with 111In-oxine or with 99mTc-HMPAO or [18F]FDG can be used in patients with suspected radiation enterocolitis. Inhibitors of the T-cell-mediated immune response, cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), and programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-1 L), also known as immunotherapy, can produce potentially fatal adverse effects due to the T-cell activation and proliferation leading to potentially autoreactive T-cells and inflammatory adverse effects across a range of tissues, contributing to immune-mediated side effects. Most of serious adverse effects with CTLA-4 inhibitors are associated with gastrointestinal tract disturbances and respiratory and urination problems. Programmed cell death protein-1 (PD-1)/PD-1 ligand (PD-1 L) serious adverse effects include colitis, hepatitis, pneumonitis, and renal failure. An improved identification of this toxicity may allow for improved treatment tailoring and clinical outcome.

Alzheimer’s disease (AD) is the main cause of dementia, with its diagnosis and management remaining challenging. Amyloid positron emission tomography (PET) has become increasingly important in medical practice for patients with AD. To integrate and update previous guidelines in the field, a task group of experts of several disciplines from multiple countries was assembled, and they revised and approved the content related to the application of amyloid PET in the medical settings of cognitively impaired individuals, focusing on clinical scenarios, patient preparation, administered activities, as well as image acquisition, processing, interpretation and reporting. In addition, expert opinions, practices, and protocols of prominent research institutions performing research on amyloid PET of dementia are integrated. With the increasing availability of amyloid PET imaging, a complete and standard pipeline for the entire examination process is essential for clinical practice. This international consensus and practice guideline will help to promote proper clinical use of amyloid PET imaging in patients with AD.

Aim to assess if the use of an audiovisual intervention in the uptake room and/or in the scanning room, could help to reduce anxiety during [18F]FDG PET/CT imaging. Methods We prospectively studied 120 patients referred for [18F]FDG PET/CT imaging. Patients were allocated in 4 groups of 30 patients depending on the use of the audiovisual intervention: (1) no audiovisual intervention; (2) audiovisual intervention only in the uptake room; (3) audiovisual intervention only in the scanning room; (4) audiovisual intervention in the uptake and the scanning rooms. In order to measure the anxiety levels of the patients before and after the scan, all patients answered the State-Trait Anxiety Inventory (STAI). Results The anxiety status across typical situations on a daily basis (STAI-T) of the 4 groups of patients was comparable with no significant differences. The mean State Anxiety (STAI-S) sum-score at prescan and postscan among groups was: (1) 17.5±8.7 vs. 17.3±8.6, p=0.834; (2) 17.4±10.5 vs. 15.8±9.6, p=0.110; (3) 17.5±11.7 vs. 15.1±9.8, p= 0.013; (4) 17.4±9.7 vs. 14.9±8.1, p= 0.009. The percentage of patients with reduction of the STAI-S score among groups 1–4 was 17%, 47%, 50%, and 66%, respectively. The variation of the percentage of patients with lower scores after intervention among groups was statistically significant (p<0.001). Conclusion Audiovisual intervention decreases anxiety levels of patients referred for PET/CT imaging. The results of our study support a beneficial effect of the audiovisual intervention and its potential to alleviate the anxiety of oncological patients who undergo a PET/CT scan.

Although there is evidence that chemotherapy can have side effects on metabolism and brain function, there are few studies on the occurrence of these side effects with immunotherapy. The present study was conducted to assess whether brain metabolic changes occur in patients with malignant melanoma under immunotherapy. Thirty-nine patients after surgical intervention and with a diagnosis of malignant melanoma were retrospectively included and were divided into two groups: one group under the first-line therapy with anti-programmed cell death-1 ± anti-cytotoxic T lymphocyte antigen-4 monoclonal antibodies and the other group without any treatment after surgery, which served as a control. Basal and follow-up whole body and brain 2-[18F]fluoro-2-deoxy-D-glucose (18F]FDG) PET/computed tomography (CT) studies were performed. Changes in brain glucose metabolism after treatment initiation of the immunotherapy group were compared with the findings in the control group. In addition, longitudinal regression analysis to investigate whether the time under immunotherapy influenced the changes of brain metabolism was performed. None of the patients presented cognitive impairment or other neurological alterations between basal and follow-up brain [18F]FDG PET/CT examinations. The statistical analysis revealed a significant relative SUV (SUVr)-loss in the left frontal region in patients of the immunotherapy group compared with the control group, with radjusted = -0.62 and P = 0.008. Severity of SUVr-loss was correlated with duration of treatment. Patients with disseminated malignant melanoma receiving immunotherapy may present a decrease of brain metabolism in the left frontal region, which is related with time-under-treatment, without any clinical evidence of neurological disorder.

Purpose Positron emission tomography (PET) with the first and only tau targeting radiotracer of ¹⁸ F-flortaucipir approved by FDA has been increasingly used in depicting tau pathology deposition and distribution in patients with cognitive impairment. The goal of this international consensus is to help nuclear medicine practitioners procedurally perform ¹⁸ F-flortaucipir PET imaging. Method A multidisciplinary task group formed by experts from various countries discussed and approved the consensus for ¹⁸ F-flortaucipir PET imaging in Alzheimer’s disease (AD), focusing on clinical scenarios, patient preparation, and administered activities, as well as image acquisition, processing, interpretation, and reporting. Conclusion This international consensus and practice guideline will help to promote the standardized use of ¹⁸ F-flortaucipir PET in patients with AD. It will become an international standard for this purpose in clinical practice.